Cartilage-derived morphogenetic protein-1 and -2 are endogenously expressed and stimulate proteoglycan synthesis in healthy and osteoarthritic human articular chondrocytes

Objective

Cartilage-derived morphogenetic protein-1 and -2 (CDMP-1 and -2) form a subgroup within the Bone morphogenetic protein family. While they are essential during embryonic joint and limb development, their role in postnatal articular cartilage is not fully clear. In this study we examined the stimulatory effects of CDMP-1 and -2 on proteoglycan synthesis and cell proliferation on postnatal human articular chondrocytes and investigated the hypothesis that osteoarthritic chondrocytes lose their responsivness to CDMP-1 and -2 compared to healthy cells and thus lead to a decrease in proteoglycan synthesis that impairs maintenance of matrix integrity.

Methods

Chondrocytes were isolated from human articular cartilage from patients with and without osteoarthritic lesions. Cell number was assessed directly after collagenase digestion and chondrocytes were cultured as monolayers for a period of seven days in a chemically defined serum-free basal medium (BM) with and without the addition of recombinant CDMP-1 and -2. The proteoglycan-synthesis rate was measured by [35S]sulfate incorporation into newly synthesized macromolecules. Growth factors influence on cell proliferation was investigated by [3H]thymidin incorporation. Using RT-PCR the endogenous expression of CDMPs and their respective type I and type II receptors was examined.

Results

Cell number per mg tissue of osteoarthritic cartilage was significantly reduced, on an average by 45%, compared to healthy controls (P < 0.007). CDMP-1 and -2 stimulation markedly increased proteoglycan synthesis in postnatal human articular chondrocytes (P < 0.05). A comparison of the biosynthetic activity between healthy and osteoarthritic samples revealed no difference, neither in stimulated nor in unstimulated cultures. [3H]thymidine incorporation showed that CDMP-1 and -2 treatment had no effect on cell proliferation. RT-PCR results indicated that CDMPs and their respective receptors are endogenously expressed not only in healthy but also in osteoarthritic cartilage.

Conclusion

The present study shows that CDMPs are potent stimulators of proteoglycan synthesis in postnatal articular chondrocytes and exert their anabolic effects on both healthy and osteoarthritic cartilagenous tissue. This data and the finding that CDMPs and their receptors are endogenously expressed in healthy and osteoarthritic cartilage suggest that osteoarthritis is not associated with a loss of responsivness to CDMP-1 and -2. Moreover the decrease in cell number seems to be important for the limited tissue repair capacity in osteoarthritis.