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. 2025 Aug;33(8):951-964.
doi: 10.1016/j.joca.2025.03.004. Epub 2025 Mar 26.

Implication of bone marrow adipose tissue in bone homeostasis during osteoarthritis

Natalia Zapata-Linares  1 , Indira Toillon  1 , Kristell Wanherdrick  1 , Audrey Pigenet  1 , Fanny Duhalde  2 , Marie Binvignat  1 , Patxi San Martin-Uriz  3 , Loïc Louvet  4 , Maria E Calleja-Cervantes  5 , Olfa Ghali Mhenni  4 , Clément Guibert  6 , Geoffroy Nourissat  1 , Alexis Nogier  7 , Damien Leterme  4 , Odile Broux  4 , Paul Magneron  1 , Felipe Prosper  8 , Christophe Chauveau  4 , Jessem Landoulsi  6 , Francis Berenbaum  9 , Juan R Rodriguez-Madoz  10 , Marie-Hélène Lafage-Proust  11 , Stéphanie Lucas  4 , Xavier Houard  12
Affiliations
Free article

Implication of bone marrow adipose tissue in bone homeostasis during osteoarthritis

Natalia Zapata-Linares et al. Osteoarthritis Cartilage. 2025 Aug.
Free article

Abstract

Objective: To explore the role of bone marrow adipocytes (BMAds) in osteoarthritis (OA).

Methods: Male and female C57BL/6 mice (n=4/group) underwent meniscectomy (MNX) or SHAM surgery. OA was determined using Osteoarthritis Research Society International (OARSI) score, and the number of perilipin+ adipocytes was quantified. Mesenchymal Stromal Cells (MSCs) from MNX and SHAM mice were differentiated into osteoblasts and adipocytes. Human adipocytes and MSCs (n=8) were enzymatically isolated from epiphyseal and metaphyseal marrow, and from subcutaneous adipose tissue (SCAT) of hip OA patients. Human OA MSCs were differentiated into osteoblasts and adipocytes (OA-Diff-hAdipo). Gene expression patterns of epiphyseal and metaphyseal BMAds, SCAT adipocytes and OA-Diff-hAdipo were evaluated by RNAseq (n=4). The effect conditioned media from OA epiphyseal bone (n=5) on the alkaline phosphatase (ALP) activity and mineralization kinetics was assessed in vitro.

Results: Increase in BMAd density was positively correlated with cartilage degradation in MNX mice. OA modified the differentiation capacity of MSCs, accelerating adipocyte differentiation and failing to produce osteoblasts in both human and mice. Human epiphyseal, metaphyseal and SCAT adipocytes from the same OA patients each displayed a specific transcriptome, suggesting different functions. Enrichment analysis defined metaphyseal OA-BMAds as cells implicated in hematopoietic stem cell differentiation. On the other hand, epiphyseal OA-BMAds were considered as osteogenic cells showing an up-regulation of genes related to bone mineralization and remodeling. Specifically, OA epiphysis-secreted molecules decreased ALP activity and altered in vitro the mineralization process.

Conclusion: All these results support the emergence of BMAds as new cell partners in OA, opening new venues for therapeutic approaches.

Keywords: Bone marrow adipose tissue; Epiphysis; Mineralization; Osteoarthritis; Subchondral bone.

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Conflict of interest statement

Conflict of interest FB reports personal fees from 4P Pharma, 4Moving Biotech, Grunenthal, GSK, Heel, Nordic Bioscience, Novartis, Servier, TRB Chemedica, Viatris outside the submitted work. NZL, IT, KW, AP, FD, MB, PSMU, LL, MECC, OGM, CG, GN, AN, DL, OB, PM, FP, CC, JL, JRRM, MHLP, SL and XH declare that they have no competing interest.

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