Total glycosides from Eucommia ulmoides seed promoted osteogenic differentiation of adipose-derived mesenchymal stem cells and bone formation in ovariectomized rats through regulating Notch signaling pathway

Abstract Background Osteoporosis (OP) is a well-known chronic degenerative disease, with impaired mesenchymal stem cells (MSCs) function and suppressed osteogenic differentiation. Total glycosides from Eucommia ulmoides seed (TGEUS) was a Chinese medicine and have rich pharmacological effects. This...

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Autores principales:	Yu-hu Zhou, Qiang Xie
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Total glycosides from Eucommia ulmoides seed Adipose‐derived mesenchymal stem cells Osteogenic differentiation Orthopedic surgery RD701-811 Diseases of the musculoskeletal system RC925-935
Acceso en línea:	https://doaj.org/article/2c8d38b5516b4dceb766c19b7c733381
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spelling	oai:doaj.org-article:2c8d38b5516b4dceb766c19b7c7333812021-11-08T11:01:41ZTotal glycosides from Eucommia ulmoides seed promoted osteogenic differentiation of adipose-derived mesenchymal stem cells and bone formation in ovariectomized rats through regulating Notch signaling pathway10.1186/s13018-021-02797-51749-799Xhttps://doaj.org/article/2c8d38b5516b4dceb766c19b7c7333812021-11-01T00:00:00Zhttps://doi.org/10.1186/s13018-021-02797-5https://doaj.org/toc/1749-799XAbstract Background Osteoporosis (OP) is a well-known chronic degenerative disease, with impaired mesenchymal stem cells (MSCs) function and suppressed osteogenic differentiation. Total glycosides from Eucommia ulmoides seed (TGEUS) was a Chinese medicine and have rich pharmacological effects. This study was designed to explore the mechanism of TGEUS in promoting osteogenic differentiation and bone formation in ovariectomized (OVX) rats. Methods Adipose‐derived mesenchymal stem cells (ADSCs) were isolated and treated with different concentration of TGEUS. Cell viability was assessed using cell counting kit-8 (CCK-8) assay. Osteogenic capacity was identified by ALP staining and ARS staining. Moreover, RNA sequencing between control and TGEUS treated ADSCs were further performed to reveal the mechanism of TGEUS in promoting osteogenic differentiation. The expression of Jag1, Lfng and Hey1 were measured using quantitative real-time polymerase chain reaction (qRTPCR). Osteogenic markers were further assessed by western blot. DAPT and NICD were further used to identify whether Notch signaling pathway involved into TGEUS promoting osteogenic differentiation of ADSCs. Ovariectomy-induced bone loss rats model was established and divided into three groups: sham, OVX and OVX + TGEUS groups. HE staining and immunohistochemical staining were further performed to identify whether TGEUS could promote bone formation. Results TGEUS treatment significantly enhanced the cell viability and ALP activity than control group, the optimal dose of TGEUS was 5 μM. We selected 5 μM TGEUS for further study. TGEUS significantly enhanced ALP activity and calcium deposition than that of control group. Activation of Notch signaling fully blocked TGEUS-induced osteogenic differentiation of ADSCs. Following TGEUS treatment, the trabecular bone of the rats was significantly increased, thickened, and more connected compared to the OVX group. With the treatment of TGEUS, the expression of Osterix (Osx), Osteocalcin (OCN) and RUNX Family Transcription Factor 2 (RUNX2) increased than OVX group. Conclusion TGEUS enhanced osteogenic differentiation of ADSCs and promoted bone formation in ovariectomy-induced bone loss rats. Our study broadened the understanding of TGEUS as a therapeutic target against osteoporosis.Yu-hu ZhouQiang XieBMCarticleTotal glycosides from Eucommia ulmoides seedAdipose‐derived mesenchymal stem cellsOsteogenic differentiationOrthopedic surgeryRD701-811Diseases of the musculoskeletal systemRC925-935ENJournal of Orthopaedic Surgery and Research, Vol 16, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Total glycosides from Eucommia ulmoides seed Adipose‐derived mesenchymal stem cells Osteogenic differentiation Orthopedic surgery RD701-811 Diseases of the musculoskeletal system RC925-935
spellingShingle	Total glycosides from Eucommia ulmoides seed Adipose‐derived mesenchymal stem cells Osteogenic differentiation Orthopedic surgery RD701-811 Diseases of the musculoskeletal system RC925-935 Yu-hu Zhou Qiang Xie Total glycosides from Eucommia ulmoides seed promoted osteogenic differentiation of adipose-derived mesenchymal stem cells and bone formation in ovariectomized rats through regulating Notch signaling pathway
description	Abstract Background Osteoporosis (OP) is a well-known chronic degenerative disease, with impaired mesenchymal stem cells (MSCs) function and suppressed osteogenic differentiation. Total glycosides from Eucommia ulmoides seed (TGEUS) was a Chinese medicine and have rich pharmacological effects. This study was designed to explore the mechanism of TGEUS in promoting osteogenic differentiation and bone formation in ovariectomized (OVX) rats. Methods Adipose‐derived mesenchymal stem cells (ADSCs) were isolated and treated with different concentration of TGEUS. Cell viability was assessed using cell counting kit-8 (CCK-8) assay. Osteogenic capacity was identified by ALP staining and ARS staining. Moreover, RNA sequencing between control and TGEUS treated ADSCs were further performed to reveal the mechanism of TGEUS in promoting osteogenic differentiation. The expression of Jag1, Lfng and Hey1 were measured using quantitative real-time polymerase chain reaction (qRTPCR). Osteogenic markers were further assessed by western blot. DAPT and NICD were further used to identify whether Notch signaling pathway involved into TGEUS promoting osteogenic differentiation of ADSCs. Ovariectomy-induced bone loss rats model was established and divided into three groups: sham, OVX and OVX + TGEUS groups. HE staining and immunohistochemical staining were further performed to identify whether TGEUS could promote bone formation. Results TGEUS treatment significantly enhanced the cell viability and ALP activity than control group, the optimal dose of TGEUS was 5 μM. We selected 5 μM TGEUS for further study. TGEUS significantly enhanced ALP activity and calcium deposition than that of control group. Activation of Notch signaling fully blocked TGEUS-induced osteogenic differentiation of ADSCs. Following TGEUS treatment, the trabecular bone of the rats was significantly increased, thickened, and more connected compared to the OVX group. With the treatment of TGEUS, the expression of Osterix (Osx), Osteocalcin (OCN) and RUNX Family Transcription Factor 2 (RUNX2) increased than OVX group. Conclusion TGEUS enhanced osteogenic differentiation of ADSCs and promoted bone formation in ovariectomy-induced bone loss rats. Our study broadened the understanding of TGEUS as a therapeutic target against osteoporosis.
format	article
author	Yu-hu Zhou Qiang Xie
author_facet	Yu-hu Zhou Qiang Xie
author_sort	Yu-hu Zhou
title	Total glycosides from Eucommia ulmoides seed promoted osteogenic differentiation of adipose-derived mesenchymal stem cells and bone formation in ovariectomized rats through regulating Notch signaling pathway
title_short	Total glycosides from Eucommia ulmoides seed promoted osteogenic differentiation of adipose-derived mesenchymal stem cells and bone formation in ovariectomized rats through regulating Notch signaling pathway
title_full	Total glycosides from Eucommia ulmoides seed promoted osteogenic differentiation of adipose-derived mesenchymal stem cells and bone formation in ovariectomized rats through regulating Notch signaling pathway
title_fullStr	Total glycosides from Eucommia ulmoides seed promoted osteogenic differentiation of adipose-derived mesenchymal stem cells and bone formation in ovariectomized rats through regulating Notch signaling pathway
title_full_unstemmed	Total glycosides from Eucommia ulmoides seed promoted osteogenic differentiation of adipose-derived mesenchymal stem cells and bone formation in ovariectomized rats through regulating Notch signaling pathway
title_sort	total glycosides from eucommia ulmoides seed promoted osteogenic differentiation of adipose-derived mesenchymal stem cells and bone formation in ovariectomized rats through regulating notch signaling pathway
publisher	BMC
publishDate	2021
url	https://doaj.org/article/2c8d38b5516b4dceb766c19b7c733381
work_keys_str_mv	AT yuhuzhou totalglycosidesfromeucommiaulmoidesseedpromotedosteogenicdifferentiationofadiposederivedmesenchymalstemcellsandboneformationinovariectomizedratsthroughregulatingnotchsignalingpathway AT qiangxie totalglycosidesfromeucommiaulmoidesseedpromotedosteogenicdifferentiationofadiposederivedmesenchymalstemcellsandboneformationinovariectomizedratsthroughregulatingnotchsignalingpathway
_version_	1718442408426864640

Total glycosides from Eucommia ulmoides seed promoted osteogenic differentiation of adipose-derived mesenchymal stem cells and bone formation in ovariectomized rats through regulating Notch signaling pathway

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