Mesenchymal Stem Cell Alterations in Bone Marrow Lesions in Patients With Hip Osteoarthritis

T. Mark Campbell, Sarah M. Churchman, Alejandro Gomez, Dennis McGonagle, Philip G. Conaghan, Frederique Ponchel, Elena Jones

In patients with osteoarthritis (OA), bone marrow lesions (BMLs) are intimately linked to disease progression. We hypothesised that aberrant multipotential stromal cell (MSC) responses within bone tissue contributed to BML pathophysiology. Therefore we investigated BML and non-BML native subchondral bone MSCs for numerical, topographic, in vitro functional and gene expression differences. Ex vivo 3T MRI was performed on femoral heads from 20 subjects with hip OA. MRI-determined BML and non-BML regions were excised and enzymatically treated to extract cells and quantify MSCs using flow cytometry and colony-forming unit-fibroblast (CFU-F) assay. Immunohistochemistry determined in vivo CD271(+) MSC distribution. Culture-expanded CD271(+) cells were analysed for tripotentiality and gene expression. BML excisions were associated with greater trabecular bone area (P=0.001) and cartilage damage (P=0.01). The CD45(-) CD271(+) MSC proportion was higher in BML than non-BML regions (median 5.6-fold; P<0.001); CFU-F assay showed a similar trend (median 4.3-fold; P=0.013). Immunohistochemistry revealed CD271(+) cell accumulation in bone adjacent to cartilage defects and areas of osteochondral angiogenesis. BML MSCs had lower proliferation and mineralization capacities in vitro and altered TNFSF11/RANKL and CXCR4/SDF-1 receptor expression. OA MSCs showed up-regulated transcripts for CXCR1 and CCR6 compared to healthy or osteoporotic bone-derived MSCs (P<0.05). This is the first study to show numerical and topographical alterations in native MSCs in diseased areas of hip OA. Given the associated functional perturbation of MSCs, these data suggest that subchondral bone MSC manipulation may be an OA treatment target. This article is protected by copyright. All rights reserved.