Bisphosphonate conjugation enhances the bone-specificity of NELL-1-based systemic therapy for spaceflight-induced bone loss in mice

Abstract Microgravity-induced bone loss results in a 1% bone mineral density loss monthly and can be a mission critical factor in long-duration spaceflight. Biomolecular therapies with dual osteogenic and anti-resorptive functions are promising for treating extreme osteoporosis. We previously confir...
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Autor*in:	Pin Ha [verfasserIn] Jin Hee Kwak [verfasserIn] Yulong Zhang [verfasserIn] Jiayu Shi [verfasserIn] Luan Tran [verfasserIn] Timothy Pan Liu [verfasserIn] Hsin-Chuan Pan [verfasserIn] Samantha Lee [verfasserIn] Jong Kil Kim [verfasserIn] Eric Chen [verfasserIn] Yasaman Shirazi-Fard [verfasserIn] Louis S. Stodieck [verfasserIn] Andy Lin [verfasserIn] Zhong Zheng [verfasserIn] Stella Nuo Dong [verfasserIn] Xinli Zhang [verfasserIn] Benjamin M. Wu [verfasserIn] Kang Ting [verfasserIn] Chia Soo [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Übergeordnetes Werk:	In: npj Microgravity - Nature Portfolio, 2016, 9(2023), 1, Seite 15
Übergeordnetes Werk:	volume:9 ; year:2023 ; number:1 ; pages:15

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1038/s41526-023-00319-7

Katalog-ID:	DOAJ091747708

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520			\|a Abstract Microgravity-induced bone loss results in a 1% bone mineral density loss monthly and can be a mission critical factor in long-duration spaceflight. Biomolecular therapies with dual osteogenic and anti-resorptive functions are promising for treating extreme osteoporosis. We previously confirmed that NELL-like molecule-1 (NELL-1) is crucial for bone density maintenance. We further PEGylated NELL-1 (NELL-polyethylene glycol, or NELL-PEG) to increase systemic delivery half-life from 5.5 to 15.5 h. In this study, we used a bio-inert bisphosphonate (BP) moiety to chemically engineer NELL-PEG into BP-NELL-PEG and specifically target bone tissues. We found conjugation with BP improved hydroxyapatite (HA) binding and protein stability of NELL-PEG while preserving NELL-1’s osteogenicity in vitro. Furthermore, BP-NELL-PEG showed superior in vivo bone specificity without observable pathology in liver, spleen, lungs, brain, heart, muscles, or ovaries of mice. Finally, we tested BP-NELL-PEG through spaceflight exposure onboard the International Space Station (ISS) at maximal animal capacity (n = 40) in a long-term (9 week) osteoporosis therapeutic study and found that BP-NELL-PEG significantly increased bone formation in flight and ground control mice without obvious adverse health effects. Our results highlight BP-NELL-PEG as a promising therapeutic to mitigate extreme bone loss from long-duration microgravity exposure and musculoskeletal degeneration on Earth, especially when resistance training is not possible due to incapacity (e.g., bone fracture, stroke).
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allfields	10.1038/s41526-023-00319-7 doi (DE-627)DOAJ091747708 (DE-599)DOAJf3f5579d49db42358eb8834e95d4a820 DE-627 ger DE-627 rakwb eng TP248.13-248.65 QP1-981 Pin Ha verfasserin aut Bisphosphonate conjugation enhances the bone-specificity of NELL-1-based systemic therapy for spaceflight-induced bone loss in mice 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Microgravity-induced bone loss results in a 1% bone mineral density loss monthly and can be a mission critical factor in long-duration spaceflight. Biomolecular therapies with dual osteogenic and anti-resorptive functions are promising for treating extreme osteoporosis. We previously confirmed that NELL-like molecule-1 (NELL-1) is crucial for bone density maintenance. We further PEGylated NELL-1 (NELL-polyethylene glycol, or NELL-PEG) to increase systemic delivery half-life from 5.5 to 15.5 h. In this study, we used a bio-inert bisphosphonate (BP) moiety to chemically engineer NELL-PEG into BP-NELL-PEG and specifically target bone tissues. We found conjugation with BP improved hydroxyapatite (HA) binding and protein stability of NELL-PEG while preserving NELL-1’s osteogenicity in vitro. Furthermore, BP-NELL-PEG showed superior in vivo bone specificity without observable pathology in liver, spleen, lungs, brain, heart, muscles, or ovaries of mice. Finally, we tested BP-NELL-PEG through spaceflight exposure onboard the International Space Station (ISS) at maximal animal capacity (n = 40) in a long-term (9 week) osteoporosis therapeutic study and found that BP-NELL-PEG significantly increased bone formation in flight and ground control mice without obvious adverse health effects. Our results highlight BP-NELL-PEG as a promising therapeutic to mitigate extreme bone loss from long-duration microgravity exposure and musculoskeletal degeneration on Earth, especially when resistance training is not possible due to incapacity (e.g., bone fracture, stroke). Biotechnology Physiology Jin Hee Kwak verfasserin aut Yulong Zhang verfasserin aut Jiayu Shi verfasserin aut Luan Tran verfasserin aut Timothy Pan Liu verfasserin aut Hsin-Chuan Pan verfasserin aut Samantha Lee verfasserin aut Jong Kil Kim verfasserin aut Eric Chen verfasserin aut Yasaman Shirazi-Fard verfasserin aut Louis S. Stodieck verfasserin aut Andy Lin verfasserin aut Zhong Zheng verfasserin aut Stella Nuo Dong verfasserin aut Xinli Zhang verfasserin aut Benjamin M. Wu verfasserin aut Kang Ting verfasserin aut Chia Soo verfasserin aut In npj Microgravity Nature Portfolio, 2016 9(2023), 1, Seite 15 (DE-627)827603568 (DE-600)2823626-9 23738065 nnns volume:9 year:2023 number:1 pages:15 https://doi.org/10.1038/s41526-023-00319-7 kostenfrei https://doaj.org/article/f3f5579d49db42358eb8834e95d4a820 kostenfrei https://doi.org/10.1038/s41526-023-00319-7 kostenfrei https://doaj.org/toc/2373-8065 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2023 1 15
spelling	10.1038/s41526-023-00319-7 doi (DE-627)DOAJ091747708 (DE-599)DOAJf3f5579d49db42358eb8834e95d4a820 DE-627 ger DE-627 rakwb eng TP248.13-248.65 QP1-981 Pin Ha verfasserin aut Bisphosphonate conjugation enhances the bone-specificity of NELL-1-based systemic therapy for spaceflight-induced bone loss in mice 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Microgravity-induced bone loss results in a 1% bone mineral density loss monthly and can be a mission critical factor in long-duration spaceflight. Biomolecular therapies with dual osteogenic and anti-resorptive functions are promising for treating extreme osteoporosis. We previously confirmed that NELL-like molecule-1 (NELL-1) is crucial for bone density maintenance. We further PEGylated NELL-1 (NELL-polyethylene glycol, or NELL-PEG) to increase systemic delivery half-life from 5.5 to 15.5 h. In this study, we used a bio-inert bisphosphonate (BP) moiety to chemically engineer NELL-PEG into BP-NELL-PEG and specifically target bone tissues. We found conjugation with BP improved hydroxyapatite (HA) binding and protein stability of NELL-PEG while preserving NELL-1’s osteogenicity in vitro. Furthermore, BP-NELL-PEG showed superior in vivo bone specificity without observable pathology in liver, spleen, lungs, brain, heart, muscles, or ovaries of mice. Finally, we tested BP-NELL-PEG through spaceflight exposure onboard the International Space Station (ISS) at maximal animal capacity (n = 40) in a long-term (9 week) osteoporosis therapeutic study and found that BP-NELL-PEG significantly increased bone formation in flight and ground control mice without obvious adverse health effects. Our results highlight BP-NELL-PEG as a promising therapeutic to mitigate extreme bone loss from long-duration microgravity exposure and musculoskeletal degeneration on Earth, especially when resistance training is not possible due to incapacity (e.g., bone fracture, stroke). Biotechnology Physiology Jin Hee Kwak verfasserin aut Yulong Zhang verfasserin aut Jiayu Shi verfasserin aut Luan Tran verfasserin aut Timothy Pan Liu verfasserin aut Hsin-Chuan Pan verfasserin aut Samantha Lee verfasserin aut Jong Kil Kim verfasserin aut Eric Chen verfasserin aut Yasaman Shirazi-Fard verfasserin aut Louis S. Stodieck verfasserin aut Andy Lin verfasserin aut Zhong Zheng verfasserin aut Stella Nuo Dong verfasserin aut Xinli Zhang verfasserin aut Benjamin M. Wu verfasserin aut Kang Ting verfasserin aut Chia Soo verfasserin aut In npj Microgravity Nature Portfolio, 2016 9(2023), 1, Seite 15 (DE-627)827603568 (DE-600)2823626-9 23738065 nnns volume:9 year:2023 number:1 pages:15 https://doi.org/10.1038/s41526-023-00319-7 kostenfrei https://doaj.org/article/f3f5579d49db42358eb8834e95d4a820 kostenfrei https://doi.org/10.1038/s41526-023-00319-7 kostenfrei https://doaj.org/toc/2373-8065 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2023 1 15
allfields_unstemmed	10.1038/s41526-023-00319-7 doi (DE-627)DOAJ091747708 (DE-599)DOAJf3f5579d49db42358eb8834e95d4a820 DE-627 ger DE-627 rakwb eng TP248.13-248.65 QP1-981 Pin Ha verfasserin aut Bisphosphonate conjugation enhances the bone-specificity of NELL-1-based systemic therapy for spaceflight-induced bone loss in mice 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Microgravity-induced bone loss results in a 1% bone mineral density loss monthly and can be a mission critical factor in long-duration spaceflight. Biomolecular therapies with dual osteogenic and anti-resorptive functions are promising for treating extreme osteoporosis. We previously confirmed that NELL-like molecule-1 (NELL-1) is crucial for bone density maintenance. We further PEGylated NELL-1 (NELL-polyethylene glycol, or NELL-PEG) to increase systemic delivery half-life from 5.5 to 15.5 h. In this study, we used a bio-inert bisphosphonate (BP) moiety to chemically engineer NELL-PEG into BP-NELL-PEG and specifically target bone tissues. We found conjugation with BP improved hydroxyapatite (HA) binding and protein stability of NELL-PEG while preserving NELL-1’s osteogenicity in vitro. Furthermore, BP-NELL-PEG showed superior in vivo bone specificity without observable pathology in liver, spleen, lungs, brain, heart, muscles, or ovaries of mice. Finally, we tested BP-NELL-PEG through spaceflight exposure onboard the International Space Station (ISS) at maximal animal capacity (n = 40) in a long-term (9 week) osteoporosis therapeutic study and found that BP-NELL-PEG significantly increased bone formation in flight and ground control mice without obvious adverse health effects. Our results highlight BP-NELL-PEG as a promising therapeutic to mitigate extreme bone loss from long-duration microgravity exposure and musculoskeletal degeneration on Earth, especially when resistance training is not possible due to incapacity (e.g., bone fracture, stroke). Biotechnology Physiology Jin Hee Kwak verfasserin aut Yulong Zhang verfasserin aut Jiayu Shi verfasserin aut Luan Tran verfasserin aut Timothy Pan Liu verfasserin aut Hsin-Chuan Pan verfasserin aut Samantha Lee verfasserin aut Jong Kil Kim verfasserin aut Eric Chen verfasserin aut Yasaman Shirazi-Fard verfasserin aut Louis S. Stodieck verfasserin aut Andy Lin verfasserin aut Zhong Zheng verfasserin aut Stella Nuo Dong verfasserin aut Xinli Zhang verfasserin aut Benjamin M. Wu verfasserin aut Kang Ting verfasserin aut Chia Soo verfasserin aut In npj Microgravity Nature Portfolio, 2016 9(2023), 1, Seite 15 (DE-627)827603568 (DE-600)2823626-9 23738065 nnns volume:9 year:2023 number:1 pages:15 https://doi.org/10.1038/s41526-023-00319-7 kostenfrei https://doaj.org/article/f3f5579d49db42358eb8834e95d4a820 kostenfrei https://doi.org/10.1038/s41526-023-00319-7 kostenfrei https://doaj.org/toc/2373-8065 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2023 1 15
allfieldsGer	10.1038/s41526-023-00319-7 doi (DE-627)DOAJ091747708 (DE-599)DOAJf3f5579d49db42358eb8834e95d4a820 DE-627 ger DE-627 rakwb eng TP248.13-248.65 QP1-981 Pin Ha verfasserin aut Bisphosphonate conjugation enhances the bone-specificity of NELL-1-based systemic therapy for spaceflight-induced bone loss in mice 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Microgravity-induced bone loss results in a 1% bone mineral density loss monthly and can be a mission critical factor in long-duration spaceflight. Biomolecular therapies with dual osteogenic and anti-resorptive functions are promising for treating extreme osteoporosis. We previously confirmed that NELL-like molecule-1 (NELL-1) is crucial for bone density maintenance. We further PEGylated NELL-1 (NELL-polyethylene glycol, or NELL-PEG) to increase systemic delivery half-life from 5.5 to 15.5 h. In this study, we used a bio-inert bisphosphonate (BP) moiety to chemically engineer NELL-PEG into BP-NELL-PEG and specifically target bone tissues. We found conjugation with BP improved hydroxyapatite (HA) binding and protein stability of NELL-PEG while preserving NELL-1’s osteogenicity in vitro. Furthermore, BP-NELL-PEG showed superior in vivo bone specificity without observable pathology in liver, spleen, lungs, brain, heart, muscles, or ovaries of mice. Finally, we tested BP-NELL-PEG through spaceflight exposure onboard the International Space Station (ISS) at maximal animal capacity (n = 40) in a long-term (9 week) osteoporosis therapeutic study and found that BP-NELL-PEG significantly increased bone formation in flight and ground control mice without obvious adverse health effects. Our results highlight BP-NELL-PEG as a promising therapeutic to mitigate extreme bone loss from long-duration microgravity exposure and musculoskeletal degeneration on Earth, especially when resistance training is not possible due to incapacity (e.g., bone fracture, stroke). Biotechnology Physiology Jin Hee Kwak verfasserin aut Yulong Zhang verfasserin aut Jiayu Shi verfasserin aut Luan Tran verfasserin aut Timothy Pan Liu verfasserin aut Hsin-Chuan Pan verfasserin aut Samantha Lee verfasserin aut Jong Kil Kim verfasserin aut Eric Chen verfasserin aut Yasaman Shirazi-Fard verfasserin aut Louis S. Stodieck verfasserin aut Andy Lin verfasserin aut Zhong Zheng verfasserin aut Stella Nuo Dong verfasserin aut Xinli Zhang verfasserin aut Benjamin M. Wu verfasserin aut Kang Ting verfasserin aut Chia Soo verfasserin aut In npj Microgravity Nature Portfolio, 2016 9(2023), 1, Seite 15 (DE-627)827603568 (DE-600)2823626-9 23738065 nnns volume:9 year:2023 number:1 pages:15 https://doi.org/10.1038/s41526-023-00319-7 kostenfrei https://doaj.org/article/f3f5579d49db42358eb8834e95d4a820 kostenfrei https://doi.org/10.1038/s41526-023-00319-7 kostenfrei https://doaj.org/toc/2373-8065 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2023 1 15
allfieldsSound	10.1038/s41526-023-00319-7 doi (DE-627)DOAJ091747708 (DE-599)DOAJf3f5579d49db42358eb8834e95d4a820 DE-627 ger DE-627 rakwb eng TP248.13-248.65 QP1-981 Pin Ha verfasserin aut Bisphosphonate conjugation enhances the bone-specificity of NELL-1-based systemic therapy for spaceflight-induced bone loss in mice 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Microgravity-induced bone loss results in a 1% bone mineral density loss monthly and can be a mission critical factor in long-duration spaceflight. Biomolecular therapies with dual osteogenic and anti-resorptive functions are promising for treating extreme osteoporosis. We previously confirmed that NELL-like molecule-1 (NELL-1) is crucial for bone density maintenance. We further PEGylated NELL-1 (NELL-polyethylene glycol, or NELL-PEG) to increase systemic delivery half-life from 5.5 to 15.5 h. In this study, we used a bio-inert bisphosphonate (BP) moiety to chemically engineer NELL-PEG into BP-NELL-PEG and specifically target bone tissues. We found conjugation with BP improved hydroxyapatite (HA) binding and protein stability of NELL-PEG while preserving NELL-1’s osteogenicity in vitro. Furthermore, BP-NELL-PEG showed superior in vivo bone specificity without observable pathology in liver, spleen, lungs, brain, heart, muscles, or ovaries of mice. Finally, we tested BP-NELL-PEG through spaceflight exposure onboard the International Space Station (ISS) at maximal animal capacity (n = 40) in a long-term (9 week) osteoporosis therapeutic study and found that BP-NELL-PEG significantly increased bone formation in flight and ground control mice without obvious adverse health effects. Our results highlight BP-NELL-PEG as a promising therapeutic to mitigate extreme bone loss from long-duration microgravity exposure and musculoskeletal degeneration on Earth, especially when resistance training is not possible due to incapacity (e.g., bone fracture, stroke). Biotechnology Physiology Jin Hee Kwak verfasserin aut Yulong Zhang verfasserin aut Jiayu Shi verfasserin aut Luan Tran verfasserin aut Timothy Pan Liu verfasserin aut Hsin-Chuan Pan verfasserin aut Samantha Lee verfasserin aut Jong Kil Kim verfasserin aut Eric Chen verfasserin aut Yasaman Shirazi-Fard verfasserin aut Louis S. Stodieck verfasserin aut Andy Lin verfasserin aut Zhong Zheng verfasserin aut Stella Nuo Dong verfasserin aut Xinli Zhang verfasserin aut Benjamin M. Wu verfasserin aut Kang Ting verfasserin aut Chia Soo verfasserin aut In npj Microgravity Nature Portfolio, 2016 9(2023), 1, Seite 15 (DE-627)827603568 (DE-600)2823626-9 23738065 nnns volume:9 year:2023 number:1 pages:15 https://doi.org/10.1038/s41526-023-00319-7 kostenfrei https://doaj.org/article/f3f5579d49db42358eb8834e95d4a820 kostenfrei https://doi.org/10.1038/s41526-023-00319-7 kostenfrei https://doaj.org/toc/2373-8065 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2023 1 15
language	English
source	In npj Microgravity 9(2023), 1, Seite 15 volume:9 year:2023 number:1 pages:15
sourceStr	In npj Microgravity 9(2023), 1, Seite 15 volume:9 year:2023 number:1 pages:15
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Biotechnology Physiology
isfreeaccess_bool	true
container_title	npj Microgravity
authorswithroles_txt_mv	Pin Ha @@aut@@ Jin Hee Kwak @@aut@@ Yulong Zhang @@aut@@ Jiayu Shi @@aut@@ Luan Tran @@aut@@ Timothy Pan Liu @@aut@@ Hsin-Chuan Pan @@aut@@ Samantha Lee @@aut@@ Jong Kil Kim @@aut@@ Eric Chen @@aut@@ Yasaman Shirazi-Fard @@aut@@ Louis S. Stodieck @@aut@@ Andy Lin @@aut@@ Zhong Zheng @@aut@@ Stella Nuo Dong @@aut@@ Xinli Zhang @@aut@@ Benjamin M. Wu @@aut@@ Kang Ting @@aut@@ Chia Soo @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	827603568
id	DOAJ091747708
language_de	englisch
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callnumber-first	T - Technology
author	Pin Ha
spellingShingle	Pin Ha misc TP248.13-248.65 misc QP1-981 misc Biotechnology misc Physiology Bisphosphonate conjugation enhances the bone-specificity of NELL-1-based systemic therapy for spaceflight-induced bone loss in mice
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topic_title	TP248.13-248.65 QP1-981 Bisphosphonate conjugation enhances the bone-specificity of NELL-1-based systemic therapy for spaceflight-induced bone loss in mice
topic	misc TP248.13-248.65 misc QP1-981 misc Biotechnology misc Physiology
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title	Bisphosphonate conjugation enhances the bone-specificity of NELL-1-based systemic therapy for spaceflight-induced bone loss in mice
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title_full	Bisphosphonate conjugation enhances the bone-specificity of NELL-1-based systemic therapy for spaceflight-induced bone loss in mice
author_sort	Pin Ha
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author_browse	Pin Ha Jin Hee Kwak Yulong Zhang Jiayu Shi Luan Tran Timothy Pan Liu Hsin-Chuan Pan Samantha Lee Jong Kil Kim Eric Chen Yasaman Shirazi-Fard Louis S. Stodieck Andy Lin Zhong Zheng Stella Nuo Dong Xinli Zhang Benjamin M. Wu Kang Ting Chia Soo
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title_sort	bisphosphonate conjugation enhances the bone-specificity of nell-1-based systemic therapy for spaceflight-induced bone loss in mice
callnumber	TP248.13-248.65
title_auth	Bisphosphonate conjugation enhances the bone-specificity of NELL-1-based systemic therapy for spaceflight-induced bone loss in mice
abstract	Abstract Microgravity-induced bone loss results in a 1% bone mineral density loss monthly and can be a mission critical factor in long-duration spaceflight. Biomolecular therapies with dual osteogenic and anti-resorptive functions are promising for treating extreme osteoporosis. We previously confirmed that NELL-like molecule-1 (NELL-1) is crucial for bone density maintenance. We further PEGylated NELL-1 (NELL-polyethylene glycol, or NELL-PEG) to increase systemic delivery half-life from 5.5 to 15.5 h. In this study, we used a bio-inert bisphosphonate (BP) moiety to chemically engineer NELL-PEG into BP-NELL-PEG and specifically target bone tissues. We found conjugation with BP improved hydroxyapatite (HA) binding and protein stability of NELL-PEG while preserving NELL-1’s osteogenicity in vitro. Furthermore, BP-NELL-PEG showed superior in vivo bone specificity without observable pathology in liver, spleen, lungs, brain, heart, muscles, or ovaries of mice. Finally, we tested BP-NELL-PEG through spaceflight exposure onboard the International Space Station (ISS) at maximal animal capacity (n = 40) in a long-term (9 week) osteoporosis therapeutic study and found that BP-NELL-PEG significantly increased bone formation in flight and ground control mice without obvious adverse health effects. Our results highlight BP-NELL-PEG as a promising therapeutic to mitigate extreme bone loss from long-duration microgravity exposure and musculoskeletal degeneration on Earth, especially when resistance training is not possible due to incapacity (e.g., bone fracture, stroke).
abstractGer	Abstract Microgravity-induced bone loss results in a 1% bone mineral density loss monthly and can be a mission critical factor in long-duration spaceflight. Biomolecular therapies with dual osteogenic and anti-resorptive functions are promising for treating extreme osteoporosis. We previously confirmed that NELL-like molecule-1 (NELL-1) is crucial for bone density maintenance. We further PEGylated NELL-1 (NELL-polyethylene glycol, or NELL-PEG) to increase systemic delivery half-life from 5.5 to 15.5 h. In this study, we used a bio-inert bisphosphonate (BP) moiety to chemically engineer NELL-PEG into BP-NELL-PEG and specifically target bone tissues. We found conjugation with BP improved hydroxyapatite (HA) binding and protein stability of NELL-PEG while preserving NELL-1’s osteogenicity in vitro. Furthermore, BP-NELL-PEG showed superior in vivo bone specificity without observable pathology in liver, spleen, lungs, brain, heart, muscles, or ovaries of mice. Finally, we tested BP-NELL-PEG through spaceflight exposure onboard the International Space Station (ISS) at maximal animal capacity (n = 40) in a long-term (9 week) osteoporosis therapeutic study and found that BP-NELL-PEG significantly increased bone formation in flight and ground control mice without obvious adverse health effects. Our results highlight BP-NELL-PEG as a promising therapeutic to mitigate extreme bone loss from long-duration microgravity exposure and musculoskeletal degeneration on Earth, especially when resistance training is not possible due to incapacity (e.g., bone fracture, stroke).
abstract_unstemmed	Abstract Microgravity-induced bone loss results in a 1% bone mineral density loss monthly and can be a mission critical factor in long-duration spaceflight. Biomolecular therapies with dual osteogenic and anti-resorptive functions are promising for treating extreme osteoporosis. We previously confirmed that NELL-like molecule-1 (NELL-1) is crucial for bone density maintenance. We further PEGylated NELL-1 (NELL-polyethylene glycol, or NELL-PEG) to increase systemic delivery half-life from 5.5 to 15.5 h. In this study, we used a bio-inert bisphosphonate (BP) moiety to chemically engineer NELL-PEG into BP-NELL-PEG and specifically target bone tissues. We found conjugation with BP improved hydroxyapatite (HA) binding and protein stability of NELL-PEG while preserving NELL-1’s osteogenicity in vitro. Furthermore, BP-NELL-PEG showed superior in vivo bone specificity without observable pathology in liver, spleen, lungs, brain, heart, muscles, or ovaries of mice. Finally, we tested BP-NELL-PEG through spaceflight exposure onboard the International Space Station (ISS) at maximal animal capacity (n = 40) in a long-term (9 week) osteoporosis therapeutic study and found that BP-NELL-PEG significantly increased bone formation in flight and ground control mice without obvious adverse health effects. Our results highlight BP-NELL-PEG as a promising therapeutic to mitigate extreme bone loss from long-duration microgravity exposure and musculoskeletal degeneration on Earth, especially when resistance training is not possible due to incapacity (e.g., bone fracture, stroke).
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title_short	Bisphosphonate conjugation enhances the bone-specificity of NELL-1-based systemic therapy for spaceflight-induced bone loss in mice
url	https://doi.org/10.1038/s41526-023-00319-7 https://doaj.org/article/f3f5579d49db42358eb8834e95d4a820 https://doaj.org/toc/2373-8065
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author2	Jin Hee Kwak Yulong Zhang Jiayu Shi Luan Tran Timothy Pan Liu Hsin-Chuan Pan Samantha Lee Jong Kil Kim Eric Chen Yasaman Shirazi-Fard Louis S. Stodieck Andy Lin Zhong Zheng Stella Nuo Dong Xinli Zhang Benjamin M. Wu Kang Ting Chia Soo
author2Str	Jin Hee Kwak Yulong Zhang Jiayu Shi Luan Tran Timothy Pan Liu Hsin-Chuan Pan Samantha Lee Jong Kil Kim Eric Chen Yasaman Shirazi-Fard Louis S. Stodieck Andy Lin Zhong Zheng Stella Nuo Dong Xinli Zhang Benjamin M. Wu Kang Ting Chia Soo
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doi_str	10.1038/s41526-023-00319-7
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up_date	2024-07-03T22:03:12.555Z
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Bisphosphonate conjugation enhances the bone-specificity of NELL-1-based systemic therapy for spaceflight-induced bone loss in mice

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