Osteoblastic PLEKHO1 contributes to joint inflammation in rheumatoid arthritisResearch in context

Background: Osteoblasts participating in the inflammation regulation gradually obtain concerns. However, its role in joint inflammation of rheumatoid arthritis (RA) is largely unknown. Here, we investigated the role of osteoblastic pleckstrin homology domain-containing family O member 1 (PLEKHO1), a...
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Autor*in:	Xiaojuan He [verfasserIn] Jin Liu [verfasserIn] Chao Liang [verfasserIn] Shaikh Atik Badshah [verfasserIn] Kang Zheng [verfasserIn] Lei Dang [verfasserIn] Baosheng Guo [verfasserIn] Defang Li [verfasserIn] Cheng Lu [verfasserIn] Qingqing Guo [verfasserIn] Danping Fan [verfasserIn] Yanqin Bian [verfasserIn] Hui Feng [verfasserIn] Lianbo Xiao [verfasserIn] Xiaohua Pan [verfasserIn] Cheng Xiao [verfasserIn] BaoTing Zhang [verfasserIn] Ge Zhang [verfasserIn] Aiping Lu [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Übergeordnetes Werk:	In: EBioMedicine - Elsevier, 2015, 41(2019), Seite 538-555
Übergeordnetes Werk:	volume:41 ; year:2019 ; pages:538-555

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1016/j.ebiom.2019.02.009

Katalog-ID:	DOAJ063840626

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520			\|a Background: Osteoblasts participating in the inflammation regulation gradually obtain concerns. However, its role in joint inflammation of rheumatoid arthritis (RA) is largely unknown. Here, we investigated the role of osteoblastic pleckstrin homology domain-containing family O member 1 (PLEKHO1), a negative regulator of osteogenic lineage activity, in regulating joint inflammation in RA. Methods: The level of osteoblastic PLEKHO1 in RA patients and collagen-induced arthritis (CIA) mice was examined. The role of osteoblastic PLEKHO1 in joint inflammation was evaluated by a CIA model and a K/BxN serum-transfer arthritis (STA) model which were induced in osteoblast-specific Plekho1 conditional knockout mice and mice expressing high Plekho1 exclusively in osteoblasts, respectively. The effect of osteoblastic PLEKHO1 inhibition was explored in a CIA mice model and a non-human primate arthritis model. The mechanism of osteoblastic PLEKHO1 in regulating joint inflammation were performed by a series of in vitro studies. Results: PLEKHO1 was highly expressed in osteoblasts from RA patients and CIA mice. Osteoblastic Plekho1 deletion ameliorated joint inflammation, whereas overexpressing Plekho1 only within osteoblasts exacerbated local inflammation in CIA mice and STA mice. PLEKHO1 was required for TRAF2-mediated RIP1 ubiquitination to activate NF-κB for inducing inflammatory cytokines production in osteoblasts. Moreover, osteoblastic PLEKHO1 inhibition diminished joint inflammation and promoted bone formation in CIA mice and non-human primate arthritis model. Conclusions: These data strongly suggest that the highly expressed PLEKHO1 in osteoblasts contributes to joint inflammation in RA. Targeting osteoblastic PLEKHO1 may exert dual therapeutic action of alleviating joint inflammation and promoting bone formation in RA. Keywords: Osteoblast, PLEKHO1, Rheumatoid arthritis, Inflammation, Bone formation
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700	0		\|a BaoTing Zhang \|e verfasserin \|4 aut
700	0		\|a Ge Zhang \|e verfasserin \|4 aut
700	0		\|a Aiping Lu \|e verfasserin \|4 aut
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author_variant	x h xh j l jl c l cl s a b sab k z kz l d ld b g bg d l dl c l cl q g qg d f df y b yb h f hf l x lx x p xp c x cx b z bz g z gz a l al
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publishDate	2019
allfields	10.1016/j.ebiom.2019.02.009 doi (DE-627)DOAJ063840626 (DE-599)DOAJ6f401d38479f46e093b866bc3f669625 DE-627 ger DE-627 rakwb eng R5-920 Xiaojuan He verfasserin aut Osteoblastic PLEKHO1 contributes to joint inflammation in rheumatoid arthritisResearch in context 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Osteoblasts participating in the inflammation regulation gradually obtain concerns. However, its role in joint inflammation of rheumatoid arthritis (RA) is largely unknown. Here, we investigated the role of osteoblastic pleckstrin homology domain-containing family O member 1 (PLEKHO1), a negative regulator of osteogenic lineage activity, in regulating joint inflammation in RA. Methods: The level of osteoblastic PLEKHO1 in RA patients and collagen-induced arthritis (CIA) mice was examined. The role of osteoblastic PLEKHO1 in joint inflammation was evaluated by a CIA model and a K/BxN serum-transfer arthritis (STA) model which were induced in osteoblast-specific Plekho1 conditional knockout mice and mice expressing high Plekho1 exclusively in osteoblasts, respectively. The effect of osteoblastic PLEKHO1 inhibition was explored in a CIA mice model and a non-human primate arthritis model. The mechanism of osteoblastic PLEKHO1 in regulating joint inflammation were performed by a series of in vitro studies. Results: PLEKHO1 was highly expressed in osteoblasts from RA patients and CIA mice. Osteoblastic Plekho1 deletion ameliorated joint inflammation, whereas overexpressing Plekho1 only within osteoblasts exacerbated local inflammation in CIA mice and STA mice. PLEKHO1 was required for TRAF2-mediated RIP1 ubiquitination to activate NF-κB for inducing inflammatory cytokines production in osteoblasts. Moreover, osteoblastic PLEKHO1 inhibition diminished joint inflammation and promoted bone formation in CIA mice and non-human primate arthritis model. Conclusions: These data strongly suggest that the highly expressed PLEKHO1 in osteoblasts contributes to joint inflammation in RA. Targeting osteoblastic PLEKHO1 may exert dual therapeutic action of alleviating joint inflammation and promoting bone formation in RA. Keywords: Osteoblast, PLEKHO1, Rheumatoid arthritis, Inflammation, Bone formation Medicine R Medicine (General) Jin Liu verfasserin aut Chao Liang verfasserin aut Shaikh Atik Badshah verfasserin aut Kang Zheng verfasserin aut Lei Dang verfasserin aut Baosheng Guo verfasserin aut Defang Li verfasserin aut Cheng Lu verfasserin aut Qingqing Guo verfasserin aut Danping Fan verfasserin aut Yanqin Bian verfasserin aut Hui Feng verfasserin aut Lianbo Xiao verfasserin aut Xiaohua Pan verfasserin aut Cheng Xiao verfasserin aut BaoTing Zhang verfasserin aut Ge Zhang verfasserin aut Aiping Lu verfasserin aut In EBioMedicine Elsevier, 2015 41(2019), Seite 538-555 (DE-627)802540074 (DE-600)2799017-5 23523964 nnns volume:41 year:2019 pages:538-555 https://doi.org/10.1016/j.ebiom.2019.02.009 kostenfrei https://doaj.org/article/6f401d38479f46e093b866bc3f669625 kostenfrei http://www.sciencedirect.com/science/article/pii/S2352396419300817 kostenfrei https://doaj.org/toc/2352-3964 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 41 2019 538-555
spelling	10.1016/j.ebiom.2019.02.009 doi (DE-627)DOAJ063840626 (DE-599)DOAJ6f401d38479f46e093b866bc3f669625 DE-627 ger DE-627 rakwb eng R5-920 Xiaojuan He verfasserin aut Osteoblastic PLEKHO1 contributes to joint inflammation in rheumatoid arthritisResearch in context 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Osteoblasts participating in the inflammation regulation gradually obtain concerns. However, its role in joint inflammation of rheumatoid arthritis (RA) is largely unknown. Here, we investigated the role of osteoblastic pleckstrin homology domain-containing family O member 1 (PLEKHO1), a negative regulator of osteogenic lineage activity, in regulating joint inflammation in RA. Methods: The level of osteoblastic PLEKHO1 in RA patients and collagen-induced arthritis (CIA) mice was examined. The role of osteoblastic PLEKHO1 in joint inflammation was evaluated by a CIA model and a K/BxN serum-transfer arthritis (STA) model which were induced in osteoblast-specific Plekho1 conditional knockout mice and mice expressing high Plekho1 exclusively in osteoblasts, respectively. The effect of osteoblastic PLEKHO1 inhibition was explored in a CIA mice model and a non-human primate arthritis model. The mechanism of osteoblastic PLEKHO1 in regulating joint inflammation were performed by a series of in vitro studies. Results: PLEKHO1 was highly expressed in osteoblasts from RA patients and CIA mice. Osteoblastic Plekho1 deletion ameliorated joint inflammation, whereas overexpressing Plekho1 only within osteoblasts exacerbated local inflammation in CIA mice and STA mice. PLEKHO1 was required for TRAF2-mediated RIP1 ubiquitination to activate NF-κB for inducing inflammatory cytokines production in osteoblasts. Moreover, osteoblastic PLEKHO1 inhibition diminished joint inflammation and promoted bone formation in CIA mice and non-human primate arthritis model. Conclusions: These data strongly suggest that the highly expressed PLEKHO1 in osteoblasts contributes to joint inflammation in RA. Targeting osteoblastic PLEKHO1 may exert dual therapeutic action of alleviating joint inflammation and promoting bone formation in RA. Keywords: Osteoblast, PLEKHO1, Rheumatoid arthritis, Inflammation, Bone formation Medicine R Medicine (General) Jin Liu verfasserin aut Chao Liang verfasserin aut Shaikh Atik Badshah verfasserin aut Kang Zheng verfasserin aut Lei Dang verfasserin aut Baosheng Guo verfasserin aut Defang Li verfasserin aut Cheng Lu verfasserin aut Qingqing Guo verfasserin aut Danping Fan verfasserin aut Yanqin Bian verfasserin aut Hui Feng verfasserin aut Lianbo Xiao verfasserin aut Xiaohua Pan verfasserin aut Cheng Xiao verfasserin aut BaoTing Zhang verfasserin aut Ge Zhang verfasserin aut Aiping Lu verfasserin aut In EBioMedicine Elsevier, 2015 41(2019), Seite 538-555 (DE-627)802540074 (DE-600)2799017-5 23523964 nnns volume:41 year:2019 pages:538-555 https://doi.org/10.1016/j.ebiom.2019.02.009 kostenfrei https://doaj.org/article/6f401d38479f46e093b866bc3f669625 kostenfrei http://www.sciencedirect.com/science/article/pii/S2352396419300817 kostenfrei https://doaj.org/toc/2352-3964 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 41 2019 538-555
allfields_unstemmed	10.1016/j.ebiom.2019.02.009 doi (DE-627)DOAJ063840626 (DE-599)DOAJ6f401d38479f46e093b866bc3f669625 DE-627 ger DE-627 rakwb eng R5-920 Xiaojuan He verfasserin aut Osteoblastic PLEKHO1 contributes to joint inflammation in rheumatoid arthritisResearch in context 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Osteoblasts participating in the inflammation regulation gradually obtain concerns. However, its role in joint inflammation of rheumatoid arthritis (RA) is largely unknown. Here, we investigated the role of osteoblastic pleckstrin homology domain-containing family O member 1 (PLEKHO1), a negative regulator of osteogenic lineage activity, in regulating joint inflammation in RA. Methods: The level of osteoblastic PLEKHO1 in RA patients and collagen-induced arthritis (CIA) mice was examined. The role of osteoblastic PLEKHO1 in joint inflammation was evaluated by a CIA model and a K/BxN serum-transfer arthritis (STA) model which were induced in osteoblast-specific Plekho1 conditional knockout mice and mice expressing high Plekho1 exclusively in osteoblasts, respectively. The effect of osteoblastic PLEKHO1 inhibition was explored in a CIA mice model and a non-human primate arthritis model. The mechanism of osteoblastic PLEKHO1 in regulating joint inflammation were performed by a series of in vitro studies. Results: PLEKHO1 was highly expressed in osteoblasts from RA patients and CIA mice. Osteoblastic Plekho1 deletion ameliorated joint inflammation, whereas overexpressing Plekho1 only within osteoblasts exacerbated local inflammation in CIA mice and STA mice. PLEKHO1 was required for TRAF2-mediated RIP1 ubiquitination to activate NF-κB for inducing inflammatory cytokines production in osteoblasts. Moreover, osteoblastic PLEKHO1 inhibition diminished joint inflammation and promoted bone formation in CIA mice and non-human primate arthritis model. Conclusions: These data strongly suggest that the highly expressed PLEKHO1 in osteoblasts contributes to joint inflammation in RA. Targeting osteoblastic PLEKHO1 may exert dual therapeutic action of alleviating joint inflammation and promoting bone formation in RA. Keywords: Osteoblast, PLEKHO1, Rheumatoid arthritis, Inflammation, Bone formation Medicine R Medicine (General) Jin Liu verfasserin aut Chao Liang verfasserin aut Shaikh Atik Badshah verfasserin aut Kang Zheng verfasserin aut Lei Dang verfasserin aut Baosheng Guo verfasserin aut Defang Li verfasserin aut Cheng Lu verfasserin aut Qingqing Guo verfasserin aut Danping Fan verfasserin aut Yanqin Bian verfasserin aut Hui Feng verfasserin aut Lianbo Xiao verfasserin aut Xiaohua Pan verfasserin aut Cheng Xiao verfasserin aut BaoTing Zhang verfasserin aut Ge Zhang verfasserin aut Aiping Lu verfasserin aut In EBioMedicine Elsevier, 2015 41(2019), Seite 538-555 (DE-627)802540074 (DE-600)2799017-5 23523964 nnns volume:41 year:2019 pages:538-555 https://doi.org/10.1016/j.ebiom.2019.02.009 kostenfrei https://doaj.org/article/6f401d38479f46e093b866bc3f669625 kostenfrei http://www.sciencedirect.com/science/article/pii/S2352396419300817 kostenfrei https://doaj.org/toc/2352-3964 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 41 2019 538-555
allfieldsGer	10.1016/j.ebiom.2019.02.009 doi (DE-627)DOAJ063840626 (DE-599)DOAJ6f401d38479f46e093b866bc3f669625 DE-627 ger DE-627 rakwb eng R5-920 Xiaojuan He verfasserin aut Osteoblastic PLEKHO1 contributes to joint inflammation in rheumatoid arthritisResearch in context 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Osteoblasts participating in the inflammation regulation gradually obtain concerns. However, its role in joint inflammation of rheumatoid arthritis (RA) is largely unknown. Here, we investigated the role of osteoblastic pleckstrin homology domain-containing family O member 1 (PLEKHO1), a negative regulator of osteogenic lineage activity, in regulating joint inflammation in RA. Methods: The level of osteoblastic PLEKHO1 in RA patients and collagen-induced arthritis (CIA) mice was examined. The role of osteoblastic PLEKHO1 in joint inflammation was evaluated by a CIA model and a K/BxN serum-transfer arthritis (STA) model which were induced in osteoblast-specific Plekho1 conditional knockout mice and mice expressing high Plekho1 exclusively in osteoblasts, respectively. The effect of osteoblastic PLEKHO1 inhibition was explored in a CIA mice model and a non-human primate arthritis model. The mechanism of osteoblastic PLEKHO1 in regulating joint inflammation were performed by a series of in vitro studies. Results: PLEKHO1 was highly expressed in osteoblasts from RA patients and CIA mice. Osteoblastic Plekho1 deletion ameliorated joint inflammation, whereas overexpressing Plekho1 only within osteoblasts exacerbated local inflammation in CIA mice and STA mice. PLEKHO1 was required for TRAF2-mediated RIP1 ubiquitination to activate NF-κB for inducing inflammatory cytokines production in osteoblasts. Moreover, osteoblastic PLEKHO1 inhibition diminished joint inflammation and promoted bone formation in CIA mice and non-human primate arthritis model. Conclusions: These data strongly suggest that the highly expressed PLEKHO1 in osteoblasts contributes to joint inflammation in RA. Targeting osteoblastic PLEKHO1 may exert dual therapeutic action of alleviating joint inflammation and promoting bone formation in RA. Keywords: Osteoblast, PLEKHO1, Rheumatoid arthritis, Inflammation, Bone formation Medicine R Medicine (General) Jin Liu verfasserin aut Chao Liang verfasserin aut Shaikh Atik Badshah verfasserin aut Kang Zheng verfasserin aut Lei Dang verfasserin aut Baosheng Guo verfasserin aut Defang Li verfasserin aut Cheng Lu verfasserin aut Qingqing Guo verfasserin aut Danping Fan verfasserin aut Yanqin Bian verfasserin aut Hui Feng verfasserin aut Lianbo Xiao verfasserin aut Xiaohua Pan verfasserin aut Cheng Xiao verfasserin aut BaoTing Zhang verfasserin aut Ge Zhang verfasserin aut Aiping Lu verfasserin aut In EBioMedicine Elsevier, 2015 41(2019), Seite 538-555 (DE-627)802540074 (DE-600)2799017-5 23523964 nnns volume:41 year:2019 pages:538-555 https://doi.org/10.1016/j.ebiom.2019.02.009 kostenfrei https://doaj.org/article/6f401d38479f46e093b866bc3f669625 kostenfrei http://www.sciencedirect.com/science/article/pii/S2352396419300817 kostenfrei https://doaj.org/toc/2352-3964 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 41 2019 538-555
allfieldsSound	10.1016/j.ebiom.2019.02.009 doi (DE-627)DOAJ063840626 (DE-599)DOAJ6f401d38479f46e093b866bc3f669625 DE-627 ger DE-627 rakwb eng R5-920 Xiaojuan He verfasserin aut Osteoblastic PLEKHO1 contributes to joint inflammation in rheumatoid arthritisResearch in context 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Osteoblasts participating in the inflammation regulation gradually obtain concerns. However, its role in joint inflammation of rheumatoid arthritis (RA) is largely unknown. Here, we investigated the role of osteoblastic pleckstrin homology domain-containing family O member 1 (PLEKHO1), a negative regulator of osteogenic lineage activity, in regulating joint inflammation in RA. Methods: The level of osteoblastic PLEKHO1 in RA patients and collagen-induced arthritis (CIA) mice was examined. The role of osteoblastic PLEKHO1 in joint inflammation was evaluated by a CIA model and a K/BxN serum-transfer arthritis (STA) model which were induced in osteoblast-specific Plekho1 conditional knockout mice and mice expressing high Plekho1 exclusively in osteoblasts, respectively. The effect of osteoblastic PLEKHO1 inhibition was explored in a CIA mice model and a non-human primate arthritis model. The mechanism of osteoblastic PLEKHO1 in regulating joint inflammation were performed by a series of in vitro studies. Results: PLEKHO1 was highly expressed in osteoblasts from RA patients and CIA mice. Osteoblastic Plekho1 deletion ameliorated joint inflammation, whereas overexpressing Plekho1 only within osteoblasts exacerbated local inflammation in CIA mice and STA mice. PLEKHO1 was required for TRAF2-mediated RIP1 ubiquitination to activate NF-κB for inducing inflammatory cytokines production in osteoblasts. Moreover, osteoblastic PLEKHO1 inhibition diminished joint inflammation and promoted bone formation in CIA mice and non-human primate arthritis model. Conclusions: These data strongly suggest that the highly expressed PLEKHO1 in osteoblasts contributes to joint inflammation in RA. Targeting osteoblastic PLEKHO1 may exert dual therapeutic action of alleviating joint inflammation and promoting bone formation in RA. Keywords: Osteoblast, PLEKHO1, Rheumatoid arthritis, Inflammation, Bone formation Medicine R Medicine (General) Jin Liu verfasserin aut Chao Liang verfasserin aut Shaikh Atik Badshah verfasserin aut Kang Zheng verfasserin aut Lei Dang verfasserin aut Baosheng Guo verfasserin aut Defang Li verfasserin aut Cheng Lu verfasserin aut Qingqing Guo verfasserin aut Danping Fan verfasserin aut Yanqin Bian verfasserin aut Hui Feng verfasserin aut Lianbo Xiao verfasserin aut Xiaohua Pan verfasserin aut Cheng Xiao verfasserin aut BaoTing Zhang verfasserin aut Ge Zhang verfasserin aut Aiping Lu verfasserin aut In EBioMedicine Elsevier, 2015 41(2019), Seite 538-555 (DE-627)802540074 (DE-600)2799017-5 23523964 nnns volume:41 year:2019 pages:538-555 https://doi.org/10.1016/j.ebiom.2019.02.009 kostenfrei https://doaj.org/article/6f401d38479f46e093b866bc3f669625 kostenfrei http://www.sciencedirect.com/science/article/pii/S2352396419300817 kostenfrei https://doaj.org/toc/2352-3964 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 41 2019 538-555
language	English
source	In EBioMedicine 41(2019), Seite 538-555 volume:41 year:2019 pages:538-555
sourceStr	In EBioMedicine 41(2019), Seite 538-555 volume:41 year:2019 pages:538-555
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Medicine R Medicine (General)
isfreeaccess_bool	true
container_title	EBioMedicine
authorswithroles_txt_mv	Xiaojuan He @@aut@@ Jin Liu @@aut@@ Chao Liang @@aut@@ Shaikh Atik Badshah @@aut@@ Kang Zheng @@aut@@ Lei Dang @@aut@@ Baosheng Guo @@aut@@ Defang Li @@aut@@ Cheng Lu @@aut@@ Qingqing Guo @@aut@@ Danping Fan @@aut@@ Yanqin Bian @@aut@@ Hui Feng @@aut@@ Lianbo Xiao @@aut@@ Xiaohua Pan @@aut@@ Cheng Xiao @@aut@@ BaoTing Zhang @@aut@@ Ge Zhang @@aut@@ Aiping Lu @@aut@@
publishDateDaySort_date	2019-01-01T00:00:00Z
hierarchy_top_id	802540074
id	DOAJ063840626
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ063840626</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230309033116.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230228s2019 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.ebiom.2019.02.009</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ063840626</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ6f401d38479f46e093b866bc3f669625</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">R5-920</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Xiaojuan He</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Osteoblastic PLEKHO1 contributes to joint inflammation in rheumatoid arthritisResearch in context</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2019</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background: Osteoblasts participating in the inflammation regulation gradually obtain concerns. However, its role in joint inflammation of rheumatoid arthritis (RA) is largely unknown. Here, we investigated the role of osteoblastic pleckstrin homology domain-containing family O member 1 (PLEKHO1), a negative regulator of osteogenic lineage activity, in regulating joint inflammation in RA. Methods: The level of osteoblastic PLEKHO1 in RA patients and collagen-induced arthritis (CIA) mice was examined. The role of osteoblastic PLEKHO1 in joint inflammation was evaluated by a CIA model and a K/BxN serum-transfer arthritis (STA) model which were induced in osteoblast-specific Plekho1 conditional knockout mice and mice expressing high Plekho1 exclusively in osteoblasts, respectively. The effect of osteoblastic PLEKHO1 inhibition was explored in a CIA mice model and a non-human primate arthritis model. The mechanism of osteoblastic PLEKHO1 in regulating joint inflammation were performed by a series of in vitro studies. Results: PLEKHO1 was highly expressed in osteoblasts from RA patients and CIA mice. Osteoblastic Plekho1 deletion ameliorated joint inflammation, whereas overexpressing Plekho1 only within osteoblasts exacerbated local inflammation in CIA mice and STA mice. PLEKHO1 was required for TRAF2-mediated RIP1 ubiquitination to activate NF-κB for inducing inflammatory cytokines production in osteoblasts. Moreover, osteoblastic PLEKHO1 inhibition diminished joint inflammation and promoted bone formation in CIA mice and non-human primate arthritis model. Conclusions: These data strongly suggest that the highly expressed PLEKHO1 in osteoblasts contributes to joint inflammation in RA. Targeting osteoblastic PLEKHO1 may exert dual therapeutic action of alleviating joint inflammation and promoting bone formation in RA. 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callnumber-first	R - Medicine
author	Xiaojuan He
spellingShingle	Xiaojuan He misc R5-920 misc Medicine misc R misc Medicine (General) Osteoblastic PLEKHO1 contributes to joint inflammation in rheumatoid arthritisResearch in context
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topic_title	R5-920 Osteoblastic PLEKHO1 contributes to joint inflammation in rheumatoid arthritisResearch in context
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title	Osteoblastic PLEKHO1 contributes to joint inflammation in rheumatoid arthritisResearch in context
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title_full	Osteoblastic PLEKHO1 contributes to joint inflammation in rheumatoid arthritisResearch in context
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author_browse	Xiaojuan He Jin Liu Chao Liang Shaikh Atik Badshah Kang Zheng Lei Dang Baosheng Guo Defang Li Cheng Lu Qingqing Guo Danping Fan Yanqin Bian Hui Feng Lianbo Xiao Xiaohua Pan Cheng Xiao BaoTing Zhang Ge Zhang Aiping Lu
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title_sort	osteoblastic plekho1 contributes to joint inflammation in rheumatoid arthritisresearch in context
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title_auth	Osteoblastic PLEKHO1 contributes to joint inflammation in rheumatoid arthritisResearch in context
abstract	Background: Osteoblasts participating in the inflammation regulation gradually obtain concerns. However, its role in joint inflammation of rheumatoid arthritis (RA) is largely unknown. Here, we investigated the role of osteoblastic pleckstrin homology domain-containing family O member 1 (PLEKHO1), a negative regulator of osteogenic lineage activity, in regulating joint inflammation in RA. Methods: The level of osteoblastic PLEKHO1 in RA patients and collagen-induced arthritis (CIA) mice was examined. The role of osteoblastic PLEKHO1 in joint inflammation was evaluated by a CIA model and a K/BxN serum-transfer arthritis (STA) model which were induced in osteoblast-specific Plekho1 conditional knockout mice and mice expressing high Plekho1 exclusively in osteoblasts, respectively. The effect of osteoblastic PLEKHO1 inhibition was explored in a CIA mice model and a non-human primate arthritis model. The mechanism of osteoblastic PLEKHO1 in regulating joint inflammation were performed by a series of in vitro studies. Results: PLEKHO1 was highly expressed in osteoblasts from RA patients and CIA mice. Osteoblastic Plekho1 deletion ameliorated joint inflammation, whereas overexpressing Plekho1 only within osteoblasts exacerbated local inflammation in CIA mice and STA mice. PLEKHO1 was required for TRAF2-mediated RIP1 ubiquitination to activate NF-κB for inducing inflammatory cytokines production in osteoblasts. Moreover, osteoblastic PLEKHO1 inhibition diminished joint inflammation and promoted bone formation in CIA mice and non-human primate arthritis model. Conclusions: These data strongly suggest that the highly expressed PLEKHO1 in osteoblasts contributes to joint inflammation in RA. Targeting osteoblastic PLEKHO1 may exert dual therapeutic action of alleviating joint inflammation and promoting bone formation in RA. Keywords: Osteoblast, PLEKHO1, Rheumatoid arthritis, Inflammation, Bone formation
abstractGer	Background: Osteoblasts participating in the inflammation regulation gradually obtain concerns. However, its role in joint inflammation of rheumatoid arthritis (RA) is largely unknown. Here, we investigated the role of osteoblastic pleckstrin homology domain-containing family O member 1 (PLEKHO1), a negative regulator of osteogenic lineage activity, in regulating joint inflammation in RA. Methods: The level of osteoblastic PLEKHO1 in RA patients and collagen-induced arthritis (CIA) mice was examined. The role of osteoblastic PLEKHO1 in joint inflammation was evaluated by a CIA model and a K/BxN serum-transfer arthritis (STA) model which were induced in osteoblast-specific Plekho1 conditional knockout mice and mice expressing high Plekho1 exclusively in osteoblasts, respectively. The effect of osteoblastic PLEKHO1 inhibition was explored in a CIA mice model and a non-human primate arthritis model. The mechanism of osteoblastic PLEKHO1 in regulating joint inflammation were performed by a series of in vitro studies. Results: PLEKHO1 was highly expressed in osteoblasts from RA patients and CIA mice. Osteoblastic Plekho1 deletion ameliorated joint inflammation, whereas overexpressing Plekho1 only within osteoblasts exacerbated local inflammation in CIA mice and STA mice. PLEKHO1 was required for TRAF2-mediated RIP1 ubiquitination to activate NF-κB for inducing inflammatory cytokines production in osteoblasts. Moreover, osteoblastic PLEKHO1 inhibition diminished joint inflammation and promoted bone formation in CIA mice and non-human primate arthritis model. Conclusions: These data strongly suggest that the highly expressed PLEKHO1 in osteoblasts contributes to joint inflammation in RA. Targeting osteoblastic PLEKHO1 may exert dual therapeutic action of alleviating joint inflammation and promoting bone formation in RA. Keywords: Osteoblast, PLEKHO1, Rheumatoid arthritis, Inflammation, Bone formation
abstract_unstemmed	Background: Osteoblasts participating in the inflammation regulation gradually obtain concerns. However, its role in joint inflammation of rheumatoid arthritis (RA) is largely unknown. Here, we investigated the role of osteoblastic pleckstrin homology domain-containing family O member 1 (PLEKHO1), a negative regulator of osteogenic lineage activity, in regulating joint inflammation in RA. Methods: The level of osteoblastic PLEKHO1 in RA patients and collagen-induced arthritis (CIA) mice was examined. The role of osteoblastic PLEKHO1 in joint inflammation was evaluated by a CIA model and a K/BxN serum-transfer arthritis (STA) model which were induced in osteoblast-specific Plekho1 conditional knockout mice and mice expressing high Plekho1 exclusively in osteoblasts, respectively. The effect of osteoblastic PLEKHO1 inhibition was explored in a CIA mice model and a non-human primate arthritis model. The mechanism of osteoblastic PLEKHO1 in regulating joint inflammation were performed by a series of in vitro studies. Results: PLEKHO1 was highly expressed in osteoblasts from RA patients and CIA mice. Osteoblastic Plekho1 deletion ameliorated joint inflammation, whereas overexpressing Plekho1 only within osteoblasts exacerbated local inflammation in CIA mice and STA mice. PLEKHO1 was required for TRAF2-mediated RIP1 ubiquitination to activate NF-κB for inducing inflammatory cytokines production in osteoblasts. Moreover, osteoblastic PLEKHO1 inhibition diminished joint inflammation and promoted bone formation in CIA mice and non-human primate arthritis model. Conclusions: These data strongly suggest that the highly expressed PLEKHO1 in osteoblasts contributes to joint inflammation in RA. Targeting osteoblastic PLEKHO1 may exert dual therapeutic action of alleviating joint inflammation and promoting bone formation in RA. Keywords: Osteoblast, PLEKHO1, Rheumatoid arthritis, Inflammation, Bone formation
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title_short	Osteoblastic PLEKHO1 contributes to joint inflammation in rheumatoid arthritisResearch in context
url	https://doi.org/10.1016/j.ebiom.2019.02.009 https://doaj.org/article/6f401d38479f46e093b866bc3f669625 http://www.sciencedirect.com/science/article/pii/S2352396419300817 https://doaj.org/toc/2352-3964
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up_date	2024-07-03T19:49:52.479Z
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fullrecord_marcxml	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ063840626</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230309033116.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230228s2019 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.ebiom.2019.02.009</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ063840626</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ6f401d38479f46e093b866bc3f669625</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">R5-920</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Xiaojuan He</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Osteoblastic PLEKHO1 contributes to joint inflammation in rheumatoid arthritisResearch in context</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2019</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background: Osteoblasts participating in the inflammation regulation gradually obtain concerns. However, its role in joint inflammation of rheumatoid arthritis (RA) is largely unknown. Here, we investigated the role of osteoblastic pleckstrin homology domain-containing family O member 1 (PLEKHO1), a negative regulator of osteogenic lineage activity, in regulating joint inflammation in RA. Methods: The level of osteoblastic PLEKHO1 in RA patients and collagen-induced arthritis (CIA) mice was examined. The role of osteoblastic PLEKHO1 in joint inflammation was evaluated by a CIA model and a K/BxN serum-transfer arthritis (STA) model which were induced in osteoblast-specific Plekho1 conditional knockout mice and mice expressing high Plekho1 exclusively in osteoblasts, respectively. The effect of osteoblastic PLEKHO1 inhibition was explored in a CIA mice model and a non-human primate arthritis model. The mechanism of osteoblastic PLEKHO1 in regulating joint inflammation were performed by a series of in vitro studies. Results: PLEKHO1 was highly expressed in osteoblasts from RA patients and CIA mice. Osteoblastic Plekho1 deletion ameliorated joint inflammation, whereas overexpressing Plekho1 only within osteoblasts exacerbated local inflammation in CIA mice and STA mice. PLEKHO1 was required for TRAF2-mediated RIP1 ubiquitination to activate NF-κB for inducing inflammatory cytokines production in osteoblasts. Moreover, osteoblastic PLEKHO1 inhibition diminished joint inflammation and promoted bone formation in CIA mice and non-human primate arthritis model. Conclusions: These data strongly suggest that the highly expressed PLEKHO1 in osteoblasts contributes to joint inflammation in RA. Targeting osteoblastic PLEKHO1 may exert dual therapeutic action of alleviating joint inflammation and promoting bone formation in RA. 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Osteoblastic PLEKHO1 contributes to joint inflammation in rheumatoid arthritisResearch in context

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