Increased Exhaustion of the Subchondral Bone-Derived Mesenchymal Stem/ Stromal Cells in Primary Versus Dysplastic Osteoarthritis.

Mesenchymal stem/ stromal cell (MSC) exhaustion has been suggested to be a hallmark of aging. Osteoarthritis has a complex etiology that comprises several factors. Dysplasia has been shown to be an individual risk factor for osteoarthritis. Subchondral bone changes are often the first detectable alterations in osteoarthritis. In this study, we aimed to determine whether skeletal MSCs are differentially affected in patients with primary versus dysplastic osteoarthritis. Patients undergoing hip arthroplasty due to primary osteoarthritis (n = 11) and osteoarthritis with hip dysplasia (n = 10) were included in the study. Femoral head subchondral bone was used for isolation of MSCs. The cells were compared using detailed ex-vivo and in-vitro analyses, which included immunophenotyping, colony-forming-unit fibroblast assay, growth kinetics, senescence, multilineage potential, immunophenotyping, and MSC marker-gene expression profiling. Isolated cells from primary osteoarthritis patients showed decreased viability in comparison with those from dysplasia patients, with similar mesenchymal fractions (i.e., CD45/ CD19/ CD14/ CD34-negative cells). In-vitro expanded MSCs from primary osteoarthritis patients showed reduced osteogenic and chondrogenic potential in comparison with dysplasia patients. There were no differences in clonogenicity, growth kinetics, senescence, adipogenic potential, and immunophenotype between these groups. Gene expression profiling showed well-known marker of bone marrow MSCs, the leptin receptor, to be significantly lower for primary osteoarthritis patients. Our study shows that the pathology of primary osteoarthritis is accompanied by bone MSC exhaustion, while biomechanical dysfunction associated with hip dysplasia can induce secondary osteoarthritis without this MSC impairment. Our study suggests that subchondral bone MSC exhaustion is implicated in the pathology of primary osteoarthritis.