PLATELET-DERIVED GROWTH-FACTOR STIMULATES CHONDROCYTE PROLIFERATION BUT PREVENTS ENDOCHONDRAL MATURATION

Platelet-derived growth factor (PDGF) is a cytokine released by platel ets at sites of injury to promote mesenchymal cell proliferation. Sinc e many bone wounds heal by endochondral bone formation, we examined th e response of chondrocytes in the endochondral lineage to PDGF. Conflu ent cultures of rat costochondral resting zone cartilage cells were in cubated with O-300 ng/mL PDGF-BB for 24 h to determine whether dose-de pendent changes in cell proliferation (cell number and [H-3]-thymidine incorporation), alkaline phosphatase specific activity, [S-35]-sulfat e incorporation, or [H-3]-proline incorporation into collagenase-diges tible protein (CDP) or noncollagenase-digestible protein (NCP), could be observed. Long-term effects of PDGF were assessed in confluent cult ures treated for 1, 2, 4, 6, 8, or 10 d with 37.5 or 150 ng/mL PDGF-BB . To determine whether PDGF-BB could induce resting zone chondrocytes to change maturation state to a growth zone chondrocyte phenotype, con fluent resting zone cell cultures were treated for 1, 2, 3, or 5 d wit h 37.5 or 150 ng/ml PDGF-BB and then challenged for an additional 24 h with 1,25-(OH)(2)D-3. PDGF-BB caused a dose-dependent increase in cel l number and [H-3]-thymidine incorporation at 24 h. The proliferative effect of the cytokine decreased with time. PDGF-BB had no effect on a lkaline phosphatase at 24 h, but at later times, the cytokine prevente d the normal increase in enzyme activity seen in post-confluent cultur es. This effect was primarily on the cells and not on the matrix. PDGF -BB stimulated [S-35]-sulfate incorporation at all times examined, but had no effect on [H-3]-proline incorporation into either the CDP or N CP pools. Thus, percent collagen production was not changed. Treatment of the cells for up to 5 d with PDGF-BB failed to elicit a 1,25-(OH)( 2)D-3 responsive phenotype typical of rat costochondral growth zone ca rtilage cells. These results show that committed chondrocytes can resp ond to PDGF-BB with increased proliferation. The effect of the cytokin e is to enhance cartilage matrix production, but at the same time to p revent progression of the cells along the endochondral maturation path way.