Academic Journal
Serum Leptin Exacerbates Osteoarthritis by Promoting Subchondral Bone H-Type Vessel Angiogenesis via Activation of the PI3K/AKT Pathway.
| Τίτλος: | Serum Leptin Exacerbates Osteoarthritis by Promoting Subchondral Bone H-Type Vessel Angiogenesis via Activation of the PI3K/AKT Pathway. |
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| Συγγραφείς: | Li R; University Town Hospital of Chongqing Medical University, Chongqing, China., Xi Z; University Town Hospital of Chongqing Medical University, Chongqing, China., Luo S; University Town Hospital of Chongqing Medical University, Chongqing, China., Qin J; University Town Hospital of Chongqing Medical University, Chongqing, China., Liu T; University Town Hospital of Chongqing Medical University, Chongqing, China., Zhang J; The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. |
| Πηγή: | Journal of cellular and molecular medicine [J Cell Mol Med] 2026 Jul; Vol. 30 (13), pp. e71232. |
| Τύπος έκδοσης: | Journal Article; Research Support, Non-U.S. Gov't |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101083777 Publication Model: Print Cited Medium: Internet ISSN: 1582-4934 (Electronic) Linking ISSN: 15821838 NLM ISO Abbreviation: J Cell Mol Med Subsets: MEDLINE |
| Imprint Name(s): | Publication: Oxford, England : Wiley-Blackwell Original Publication: Bucharest : "Carol Davila" University Press, 2000- |
| Ιατρικοί όροι (MeSH): | Leptin*/blood , Phosphatidylinositol 3-Kinases*/metabolism , Proto-Oncogene Proteins c-akt*/metabolism , Osteoarthritis*/pathology , Osteoarthritis*/blood , Neovascularization, Pathologic*/pathology , Neovascularization, Pathologic*/blood , Bone and Bones*/pathology , Bone and Bones*/blood supply , Bone and Bones*/metabolism , Angiogenesis*, Mesenchymal Stem Cells/metabolism ; Receptors, Leptin/metabolism ; Animals ; Humans ; Signal Transduction ; Mice ; Male ; Mice, Knockout ; Osteogenesis ; Mice, Inbred C57BL ; Female |
| Περίληψη: | Osteoarthritis (OA) is a common degenerative joint disease closely associated with obesity. Adipokines secreted by adipose tissue play critical roles in disease progression. This study focuses on the adipokine leptin and investigates its relationship with knee osteoarthritis. Analysis of subchondral bone tissue from OA patients revealed decreased leptin receptor expression, enhanced osteogenic activity, and a significant increase in H-type vessel number. Concurrently, serum leptin levels were markedly elevated in OA patients. Animal experiments further demonstrated that leptin-knockout obese mice exhibited significantly milder OA, reduced H-type vessel formation, and decreased osteogenic activity. In contrast, mice with high serum leptin levels showed more severe joint destruction and vascular hyperplasia. In vitro cell experiments indicated that leptin activates the PI3K/AKT signalling pathway in bone marrow mesenchymal stem cells (BMSCs), increasing the secretion of angiogenic factors such as VEGF and HIF-1α. Conditioned medium from leptin-treated BMSCs promoted tube formation and expression of H-type vessel markers (EMCN/CD31) in mouse umbilical vein endothelial cells. Inhibition of the PI3K pathway using Ly294002 in BMSCs or ZSTK474 in mice abolished leptin's effects. These results suggest that obesity-induced hyperleptinemia drives aberrant H-type vessel angiogenesis and active bone remodelling in subchondral bone via the PI3K/AKT pathway, thereby accelerating OA progression. (© 2026 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.) |
| Σχόλια: | Erratum in: J Cell Mol Med. 2026 Oct;30(19):e71376. doi: 10.1111/jcmm.71376.. (PMID: 42834867) |
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| Grant Information: | 2025MSXM087 Chongqing Science and Health Joint Medical Research Project; CSTB2023NSCQ-MSX0640 Natural Science Foundation Project of Chongqing, Chongqing Science and Technology Commission; 2025MSXM081 Chongqing Municipal Health Commission |
| Contributed Indexing: | Keywords: H‐type vessels; PI3K‐AKT Signalling pathway; leptin; osteoarthritis; subchondral bone |
| Substance Nomenclature: | 0 (Leptin) EC 2.7.1.- (Phosphatidylinositol 3-Kinases) EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) 0 (Receptors, Leptin) |
| Entry Date(s): | Date Created: 20260630 Date Completed: 20260630 Latest Revision: 20261006 |
| Update Code: | 20261006 |
| PubMed Central ID: | PMC13314715 |
| DOI: | 10.1111/jcmm.71232 |
| PMID: | 42374652 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1582-4934 |
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| DOI: | 10.1111/jcmm.71232 |