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The IFT80/Hedgehog Pathway Regulates the Osteogenic-adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells.
Jiang, Mingyang; Zhang, Ke; Hu, Yang; Lu, Shenyi; Wei, Guiqing; Liu, Kaicheng; Chen, Chuanliang; Zou, Xiaochong; Dai, Yongheng; Gui, Ying; Wu, Jing; Bo, Huan; Bo, Zhandong.
Afiliación
  • Jiang M; Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • Zhang K; Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • Hu Y; Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • Lu S; Department of Rehabilitation, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
  • Wei G; Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • Liu K; Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • Chen C; Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • Zou X; Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • Dai Y; Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • Gui Y; Clinical Laboratory Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • Wu J; Clinical Laboratory Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • Bo H; International Division of Nanning No. 2 High School, Nanning, China.
  • Bo Z; Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Curr Med Chem ; 2024 Apr 18.
Article en En | MEDLINE | ID: mdl-38644709
ABSTRACT

BACKGROUND:

Steroid-induced avascular necrosis of the femoral head (SANFH) is a typical refractory disease that often progresses irreversibly and has a high disability rate. Numerous studies have confirmed that abnormal osteogenic-adipogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) is one of the major factors of SANFH. However, the mechanism remains to be elucidated.

OBJECTIVES:

This study aimed to investigate the mechanism and effect of the IFT80/Hedgehog-mediated osteogenic-adipogenic differentiation of BM-MSCs in SANFH.

METHODS:

Femoral head specimens of SANFH patients and femoral neck fractures (FNF) patients were collected to detect the expression of IFT80, Shh and osteogenic-adipogenic differentiation-related genes by immunohistochemistry (IHC), western blot (WB) and Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR). Based on the rabbit SANFH model, the mRNA expression and protein level of IFT80 and Shh were detected by RT-qPCR and WB. After the osteogenic/adipogenic differentiation based on rabbit BM-MSCs, the IFT80, Gli1, PPAR-γ, and Runx2 expression were detected. Differences in alkaline phosphodiesterase activity, calcium nodule, quantification/distribution of lipid droplets, expression of IFT80/Hedgehog axis, and the level of osteogenic- adipogenic associated factors were determined after IFT80 overexpression.

RESULTS:

RT-qPCR, WB and IHC revealed that IFT80 and Shh lowly expressed in the osteoblasts and intra-trabecular osteocytes at the edge of trabeculae and in the intercellular matrix of the bone marrow lumen in the SANFH specimens. The Runx2 expression was low, while the PPAR-γ expression was high in both human specimens and animal models of SANFH, suggesting that the balance of osteogenic-adipogenic differentiation was dysregulated. Rabbit BM-MSCs with stable overexpression of IFT80 showed increased alkaline phosphatase activity after induction of osteogenic differentiation, increased calcium nodule production, and decreased adipogenesis after induction of adipogenic differentiation.

CONCLUSION:

There is a dysregulation of the balance of osteogenic-adipogenic differentiation in SANFH. IFT80 may inhibit adipogenic differentiation while promoting osteogenic differentiation in rabbit BM-MSCs by activating the Hedgehog pathway.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Curr Med Chem Asunto de la revista: QUIMICA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Emiratos Árabes Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Curr Med Chem Asunto de la revista: QUIMICA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Emiratos Árabes Unidos