Recent advances in osteonecrosis of the femoral head: a focus on mesenchymal stem cells and adipocytes

Abstract Osteonecrosis of the femoral head (ONFH) is a debilitating orthopedic disease characterized by femoral head collapse and destruction of bone and articular cartilage, resulting in severe joint pain and loss of hip mobility. Bone marrow mesenchymal stem cells (BMSCs) exhibit multilineage diff...

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Main Authors: Shilei Zhang, Haojue Wang, Qi Meng, Wayne Yuk-wai Lee, Ziqing Li, Shui Sun
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Journal of Translational Medicine
Subjects:
Online Access:https://doi.org/10.1186/s12967-025-06564-6
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author Shilei Zhang
Haojue Wang
Qi Meng
Wayne Yuk-wai Lee
Ziqing Li
Shui Sun
author_facet Shilei Zhang
Haojue Wang
Qi Meng
Wayne Yuk-wai Lee
Ziqing Li
Shui Sun
author_sort Shilei Zhang
collection DOAJ
description Abstract Osteonecrosis of the femoral head (ONFH) is a debilitating orthopedic disease characterized by femoral head collapse and destruction of bone and articular cartilage, resulting in severe joint pain and loss of hip mobility. Bone marrow mesenchymal stem cells (BMSCs) exhibit multilineage differentiation potential, including osteoblasts, adipocytes, fibroblasts, chondrocytes, and neurocytes. The imbalance between osteogenesis and adipogenesis in BMSCs plays a critical role in ONFH pathogenesis. Factors such as alcohol consumption and glucocorticoid exposure promote adipogenic differentiation while inhibiting osteogenic differentiation, leading to excessive adipocyte accumulation, reduced bone formation, and vascular impairment. We highlight the molecular mechanisms underlying ONFH with a particular focus on the role of BMSCs and further discuss the involvement of adipocytes. Moreover, we suggest that the use of adipose-derived mesenchymal stem cells (ADMSCs) is a viable approach for stem cell therapy and may have immense potential in ONFH. Several signaling pathways, including the Wnt, TGFβ/BMP, and PI3K/AKT pathways, along with various RNAs and other regulators, govern the osteogenesis and adipogenesis of BMSCs. These signaling pathways target essential transcription factors, such as Runx2 for osteogenesis and PPARγ and C/EBPs for adipogenesis. Adipocytes and their secreted adipokines, including leptin and adiponectin, strongly influence ONFH progression. Emerging therapies involving ADMSCs show potential for promoting bone regeneration and neovascularization. Our review provides a comprehensive overview of the current understanding of ONFH mechanisms by focusing on mesenchymal stem cells and adipocytes and suggests future research directions for therapeutic interventions.
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spelling doaj-art-df2dc201de9d420dadcafb997dd7cb7c2025-08-20T02:03:38ZengBMCJournal of Translational Medicine1479-58762025-05-0123111410.1186/s12967-025-06564-6Recent advances in osteonecrosis of the femoral head: a focus on mesenchymal stem cells and adipocytesShilei Zhang0Haojue Wang1Qi Meng2Wayne Yuk-wai Lee3Ziqing Li4Shui Sun5Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityDepartment of Joint Surgery, Cheeloo College of Medicine, Shandong Provincial Hospital, Shandong UniversityDepartment of Joint Surgery, Cheeloo College of Medicine, Shandong Provincial Hospital, Shandong UniversityDepartment of Orthopaedics and Traumatology, The Chinese University of Hong KongDepartment of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityDepartment of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityAbstract Osteonecrosis of the femoral head (ONFH) is a debilitating orthopedic disease characterized by femoral head collapse and destruction of bone and articular cartilage, resulting in severe joint pain and loss of hip mobility. Bone marrow mesenchymal stem cells (BMSCs) exhibit multilineage differentiation potential, including osteoblasts, adipocytes, fibroblasts, chondrocytes, and neurocytes. The imbalance between osteogenesis and adipogenesis in BMSCs plays a critical role in ONFH pathogenesis. Factors such as alcohol consumption and glucocorticoid exposure promote adipogenic differentiation while inhibiting osteogenic differentiation, leading to excessive adipocyte accumulation, reduced bone formation, and vascular impairment. We highlight the molecular mechanisms underlying ONFH with a particular focus on the role of BMSCs and further discuss the involvement of adipocytes. Moreover, we suggest that the use of adipose-derived mesenchymal stem cells (ADMSCs) is a viable approach for stem cell therapy and may have immense potential in ONFH. Several signaling pathways, including the Wnt, TGFβ/BMP, and PI3K/AKT pathways, along with various RNAs and other regulators, govern the osteogenesis and adipogenesis of BMSCs. These signaling pathways target essential transcription factors, such as Runx2 for osteogenesis and PPARγ and C/EBPs for adipogenesis. Adipocytes and their secreted adipokines, including leptin and adiponectin, strongly influence ONFH progression. Emerging therapies involving ADMSCs show potential for promoting bone regeneration and neovascularization. Our review provides a comprehensive overview of the current understanding of ONFH mechanisms by focusing on mesenchymal stem cells and adipocytes and suggests future research directions for therapeutic interventions.https://doi.org/10.1186/s12967-025-06564-6Osteonecrosis of the femoral headMesenchymal stem cellAdipocyteSignaling pathwaysAdipokine
spellingShingle Shilei Zhang
Haojue Wang
Qi Meng
Wayne Yuk-wai Lee
Ziqing Li
Shui Sun
Recent advances in osteonecrosis of the femoral head: a focus on mesenchymal stem cells and adipocytes
Journal of Translational Medicine
Osteonecrosis of the femoral head
Mesenchymal stem cell
Adipocyte
Signaling pathways
Adipokine
title Recent advances in osteonecrosis of the femoral head: a focus on mesenchymal stem cells and adipocytes
title_full Recent advances in osteonecrosis of the femoral head: a focus on mesenchymal stem cells and adipocytes
title_fullStr Recent advances in osteonecrosis of the femoral head: a focus on mesenchymal stem cells and adipocytes
title_full_unstemmed Recent advances in osteonecrosis of the femoral head: a focus on mesenchymal stem cells and adipocytes
title_short Recent advances in osteonecrosis of the femoral head: a focus on mesenchymal stem cells and adipocytes
title_sort recent advances in osteonecrosis of the femoral head a focus on mesenchymal stem cells and adipocytes
topic Osteonecrosis of the femoral head
Mesenchymal stem cell
Adipocyte
Signaling pathways
Adipokine
url https://doi.org/10.1186/s12967-025-06564-6
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