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Loss of BACH1 improves osteogenic differentiation in glucocorticoid-induced hBMSCs through restoring autophagy.
Xiao, ShuYing; Li, GuoJuan; Tan, MeiHua; Liu, Wen; Li, WenJin.
Afiliación
  • Xiao S; Department of Endocrinology, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, NO. 336, Dongfeng South Road, Zhuhui District, Hengyang, Hunan Province, 421002, China.
  • Li G; Department of Endocrinology, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, NO. 336, Dongfeng South Road, Zhuhui District, Hengyang, Hunan Province, 421002, China.
  • Tan M; Department of Endocrinology, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, NO. 336, Dongfeng South Road, Zhuhui District, Hengyang, Hunan Province, 421002, China.
  • Liu W; Department of Endocrinology, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, NO. 336, Dongfeng South Road, Zhuhui District, Hengyang, Hunan Province, 421002, China.
  • Li W; Department of Nutrition, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China. 278244750@qq.com.
BMC Musculoskelet Disord ; 25(1): 665, 2024 Aug 24.
Article en En | MEDLINE | ID: mdl-39182017
ABSTRACT

BACKGROUND:

Glucocorticoid-induced osteoporosis (GIOP) is the most common type of secondary osteoporosis. Recently, autophagy has been found to be related with the development of various diseases, including osteoporosis and osteoblast differentiation regulations. BTB and CNC homology 1 (BACH1) was a previously confirmed regulator for osteoblast differentiation, but whether it's could involve in glucocorticoid-induced human bone mesenchymal stem cells (hBMSCs) differentiation and autophagy regulation remain not been elucidated.

METHODS:

hBMSCs were identified by flow cytometry method, and its differentiation ability were measured by ARS staining, oil O red, and Alcian blue staining assays. Gene and proteins were quantified via qRT-PCR and western blot assays, respectively. Autophagy activity was determined using immunofluorescence. ChIP and dual luciferase assay validated the molecular interactions.

RESULTS:

The data revealed that isolated hBMSCs exhibited positive of CD29/CD44 and negative CD45/CD34. Moreover, BACH1 was abated gradually during osteoblast differentiation of hBMSCs, while dexamethasone (Dex) treatment led to BACH1 upregulation. Loss of BACH1 improved osteoblast differentiation and activated autophagy activity in Dex-challenged hBMSCs. Autophagy-related proteins (ATG3, ATG4, ATG5, ATG7, ATG12) were repressed after Dex treatment, while ATG3, ATG7 and BECN1 could be elevated by BACH1 knockdown, especially ATG7. Moreover, BACH1 could interact ATG7 promoter region to inhibit its transcription. Co-inhibition of ATG7 greatly overturned the protective roles of BACH1 loss on osteoblast differentiation and autophagy in Dex-induced hBMSCs.

CONCLUSION:

Taken together, our results demonstrated that silencing of BACH1 mitigated Dex-triggered osteogenic differentiation inhibition by transcriptionally activating ATG7-mediated autophagy, suggesting that BACH1 may be a therapeutic target for GIOP treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoblastos / Osteogénesis / Autofagia / Dexametasona / Diferenciación Celular / Factores de Transcripción con Cremalleras de Leucina de Carácter Básico / Células Madre Mesenquimatosas / Glucocorticoides Límite: Humans Idioma: En Revista: BMC Musculoskelet Disord Asunto de la revista: FISIOLOGIA / ORTOPEDIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoblastos / Osteogénesis / Autofagia / Dexametasona / Diferenciación Celular / Factores de Transcripción con Cremalleras de Leucina de Carácter Básico / Células Madre Mesenquimatosas / Glucocorticoides Límite: Humans Idioma: En Revista: BMC Musculoskelet Disord Asunto de la revista: FISIOLOGIA / ORTOPEDIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido