Chondrocyte differentiation in human osteoarthritis: Expression of osteocalcin in normal and osteoarthritic cartilage and bone

Osteocalcin (OC), which is a marker of the mature osteoblasts, can also be found in posthypertrophic chondrocytes of the epiphyseal growth plate, but not in chondtocytes of the resting zone or in adult cartilage. In human ost eoarthritis (OA), chondrocytes can differentiate to a hypertrophic phenotyp e characterized by type X collagen. The protein- and mRNA-expression patter n of OC was systematically analyzed in decalcified cartilage and bone secti ons and nondecalcified cartilage sections of human osteoarthritic knee join ts with different stages of OA to investigate the differentiation of chondr ocytes in OA. In severe OA, we found an enhanced expression of the OC mRNA in the subchondral bone plate, demonstrating an increased osteoblast activi ty. Interestingly, the OC protein and OC mRNA were also detected in osteoar thritic chondrocytes, whereas in chondrocytes of normal adult cartilage, bo th the protein staining and the specific mRNA signal were negative. The OC mRNA signal increased with the severity of OA and chondrocytes from the dee p cartilage layer, and proliferating chondrocytes from clusters showed the strongest signal for OC mRNA. In this late stage of OA, chondrocytes also s tained for alkaline phosphatase and type X collagen. Our results clearly sh ow that the expression of OC in chondrocytes correlates with chondrocyte hy pertrophy in OA. Although the factors including this phenotypic shift in OA are still unknown, it can be assumed that the altered microenvironment aro und osteoarthritic chondrocytes and systemic mediators could be potential i nducers of this differentiation.