REGIONAL MITOGENIC RESPONSE OF THE MENISCUS TO PLATELET-DERIVED GROWTH-FACTOR (PDGF-AB)

Since meniscal healing is region-specific, we studied the regional (pe ripheral compared with central) response of meniscal explants to human , recombinant platelet-derived growth factor-AB. Meniscal explants fro m the hindlimbs of both knees of mature sheep were sectioned and were cultured with variable doses of human, recombinant platelet-derived gr owth factor-AB, and incorporation of [H-3]-thymidine was measured. The mitogenic response was measured at different times in culture (48 or 96 hours) and by location (lateral or medial). In the absence of the g rowth factor, the peripheral third of both menisci incorporated 10-fol d more [H-3]-thymidine on a weight basis than did the central two-thir ds. Cellularity was equivalent in the two regions. Doses of less than 100 ng/ml of growth factor produced either no stimulation or a variabl e response. A dose of 100 ng/ml resulted in consistent, significant (p < 0.05) stimulation in all groups in the peripheral region, and a dos e of 200 ng/ml provided more than a 2.5-fold increase. Multiple-factor analysis of variance demonstrated that there were no significant diff erences between experiments, times in culture, or menisci. The central region did not respond to stimulation with the growth factor at any o f the doses tested. These data suggest that regional differences (peri pheral compared with central) in responsiveness to human, recombinant platelet-derived growth factor-AB may reflect a different level of sig nal transduction machinery for growth factor receptors and distinct fi brochondrocyte populations. These findings are consistent with the var iable healing capacity of the meniscal regions in vivo and suggest a p harmacological means to promote the repair of the peripheral meniscal region.