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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2025-05-01
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| Series: | Journal of Translational Medicine |
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| 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 |
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| 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. |
| format | Article |
| id | doaj-art-df2dc201de9d420dadcafb997dd7cb7c |
| institution | OA Journals |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-05-01 |
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| series | Journal of Translational Medicine |
| 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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