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Regional mitogenic response of the meniscus to platelet-derived growth factor (PDGF-AB)
K P Spindler1, C E Mayes, R R Miller
1Department of Orthopaedics and Rehabilitation, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Abstract:
Since meniscal healing is region-specific, we studied the regional (peripheral compared with central) response of meniscal explants to human, recombinant platelet-derived growth factor-AB. Meniscal explants from the hindlimbs of both knees of mature sheep were sectioned and were cultured with variable doses of human, recombinant platelet-derived growth factor-AB, and incorporation of [3H]-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 growth factor, the peripheral third of both menisci incorporated 10-fold more [3H]-thymidine on a weight basis than did the central two-thirds. Cellularity was equivalent in the two regions. Doses of less than 100 ng/ml of growth factor produced either no stimulation or a variable response. A dose of 100 ng/ml resulted in consistent, significant (p < 0.05) stimulation in all groups in the peripheral region, and a dose of 200 ng/ml provided more than a 2.5-fold increase. Multiple-factor analysis of variance demonstrated that there were no significant differences between experiments, times in culture, or menisci. The central region did not respond to stimulation with the growth factor at any of the doses tested. These data suggest that regional differences (peripheral compared with central) in responsiveness to human, recombinant platelet-derived growth factor-AB may reflect a different level of signal transduction machinery for growth factor receptors and distinct fibrobchondrocyte populations. These findings are consistent with the variable healing capacity of the meniscal regions in vivo and suggest a pharmacological means to promote the repair of the peripheral meniscal region.
Insights
Peripheral meniscus tissue shows a significant mitogenic response to platelet-derived growth factor-AB, unlike the central region. This suggests targeted growth factor therapy could enhance healing in specific meniscal areas.
Area of Science:
- Orthopedics
- Regenerative Medicine
- Biochemistry
Background:
- Meniscal healing capacity varies significantly between peripheral and central regions.
- Understanding the cellular response to growth factors is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the regional (peripheral vs. central) response of ovine meniscal explants to human, recombinant platelet-derived growth factor-AB (rhPDGF-AB).
- To determine the optimal dose of rhPDGF-AB for stimulating meniscal cell proliferation.
Main Methods:
- Ovine meniscal explants were cultured with varying doses of rhPDGF-AB.
- Incorporation of [3H]-thymidine was measured to assess mitogenic response.
- Responses were analyzed based on meniscal region (peripheral vs. central) and culture time (48 or 96 hours).
Main Results:
- The peripheral meniscus incorporated 10-fold more [3H]-thymidine than the central region in the absence of growth factor.
- A dose of 100 ng/ml rhPDGF-AB significantly stimulated proliferation in the peripheral region, with 200 ng/ml yielding a 2.5-fold increase.
- The central meniscal region showed no significant response to rhPDGF-AB at any tested concentration.
Conclusions:
- Regional differences in meniscal responsiveness to rhPDGF-AB suggest distinct signal transduction pathways and cell populations.
- These findings support the concept of targeted pharmacological interventions to promote healing in the avascular peripheral meniscus.
- The study highlights the potential of rhPDGF-AB for enhancing meniscal repair in specific regions.