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Tumour necrosis factor α regulates the miR-27a-3p-Sfrp1 axis in a mouse model of osteoporosis.
Zhang, Dang-Feng; Jin, Xiao-Na; Ma, Xing; Qiu, Yu-Sheng; Ma, Wei; Dai, Xing; Zhang, Zhi.
Afiliación
  • Zhang DF; Department of Orthopedics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
  • Jin XN; Department of Nursing, Xi'an International University, Xi'an, Shaanxi, China.
  • Ma X; Department of Orthopedics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
  • Qiu YS; Department of Orthopedics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
  • Ma W; Department of Orthopedics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
  • Dai X; Department of Orthopedics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
  • Zhang Z; Department of Orthopedics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Exp Physiol ; 109(7): 1109-1123, 2024 Jul.
Article en En | MEDLINE | ID: mdl-38748896
ABSTRACT
Osteoporosis is a metabolic bone disease that involves gradual loss of bone density and mass, thus resulting in increased fragility and risk of fracture. Inflammatory cytokines, such as tumour necrosis factor α (TNF-α), inhibit osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and several microRNAs are implicated in osteoporosis development. This study aimed to explore the correlation between TNF-α treatment and miR-27a-3p expression in BMSC osteogenesis and further understand their roles in osteoporosis. An osteoporosis animal model was established using ovariectomized (OVX) mice. Compared with Sham mice, the OVX mice had a significantly elevated level of serum TNF-α and decreased level of bone miR-27a-3p, and in vitro TNF-α treatment inhibited miR-27a-3p expression in BMSCs. In addition, miR-27a-3p promoted osteogenic differentiation of mouse BMSCs in vitro, as evidenced by alkaline phosphatase staining and Alizarin Red-S staining, as well as enhanced expression of the osteogenic markers Runx2 and Osterix. Subsequent bioinformatics analysis combined with experimental validation identified secreted frizzled-related protein 1 (Sfrp1) as a downstream target of miR-27a-3p. Sfrp1 overexpression significantly inhibited the osteogenic differentiation of BMSCs in vitro and additional TNF-α treatment augmented this inhibition. Moreover, Sfrp1 overexpression abrogated the promotive effect of miR-27a-3p on the osteogenic differentiation of BMSCs. Furthermore, the miR-27a-3p-Sfrp1 axis was found to exert its regulatory function in BMSC osteogenic differentiation via regulating Wnt3a-ß-catenin signalling. In summary, this study revealed that TNF-α regulated a novel miR-27a-3p-Sfrp1 axis in osteogenic differentiation of BMSCs. The data provide new insights into the development of novel therapeutic strategies for osteoporosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteogénesis / Osteoporosis / Ovariectomía / Diferenciación Celular / Factor de Necrosis Tumoral alfa / MicroARNs / Modelos Animales de Enfermedad / Células Madre Mesenquimatosas Límite: Animals Idioma: En Revista: Exp Physiol Asunto de la revista: FISIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteogénesis / Osteoporosis / Ovariectomía / Diferenciación Celular / Factor de Necrosis Tumoral alfa / MicroARNs / Modelos Animales de Enfermedad / Células Madre Mesenquimatosas Límite: Animals Idioma: En Revista: Exp Physiol Asunto de la revista: FISIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido