Purpose: Damage to articular cartilage leads to an incomplete healing response. This has elicited interest in improving the understanding of chondrocyte biology and finding ways to stimulate a more effective repair response. Neuropeptides play a role in the proliferative and reparative processes of many tissue types, but little is known about their effects on articular cartilage. This research aimed to investigate the effect of four neuropeptides on articular chondrocytes.

Method: Bovine chondrocytes were cultivated in monolayer culture in media alone or media containing one of four neuropeptides: NPY, CGRP, SP, and VIP. Enzymatically digested chondrocytes from the articular surface of the femoral trochlea, femoral condyles, and patella of freshly slaughtered veal (n=8) were plated at 1×10^5 cells/mL in DMEM complete media with 5% FCS. Proliferation and proteoglycan assays were conducted at days 2,4,6, and 8.

Results: Substance P showed a statistically significant stimulatory effect on chondrocyte proliferation and proteoglycan production that was greatest at a concentration of 5 μg/ml. NPY and VIP showed a dose dependent suppressive effect on chondrocyte proliferation that was greatest at their highest concentrations and was significant at all time points, with the exception of VIP at day 2. CGRP showed no significant effect on proliferation or proteoglycan production.

Conclusion: Substance P showed a reliable stimulation of chondrocyte proliferation and proteoglycan production while NPY and VIP showed dose-dependent depressive effects. These findings support the idea that the peripheral nervous system, through neuropeptides, exerts direct influence on articular chondrocytes. This may provide some insight into the pathophysiology of inflammatory and degenerative arthritis and provide targets for modifying the repair response of articular cartilage.

Purpose: Osteoarthritis (OA) is the most common form of arthritis in the United States and according to the National Institutes of Health, affects over 21 million people. This degenerative joint disease has repeatedly been linked to obesity. It is hypothesized that obesity, defined as a body mass index (BMI) over 30 kg/m2, increases the incidence of OA through increased joint pressure and disruption of normal metabolism. The actual changes in metabolism resulting from obesity and possibly preceding OA have not been thoroughly investigated. The purpose of this study was to identify the relationship between chondrocyte metabolism and BMI in osteoarthritic tissue.

Method: Grade 0 or 1 cartilage was removed from the medial and/or lateral femoral condyles after total knee arthroplasty. Isolated chondrocytes were then resus-pended in alginate beads at 2×106 cells/mL. The beads were equilibrated in media containing 10% fetal bovine serum for 7 days (37°C) and then separated into wells (8 beads/well) with 1 mL media. Media was replaced every 48 hours. At day 5, 9, and 13 days, glycosamino-glycan (GAG) content was measured in the cell pellet, alginate, and saved media using the dimethylmethylene blue (DMMB) assay. The DMMB results were normalized to DNA content. All procedures were approved by the University of Wisconsin – Madison, Institutional Review Board.

Results: At day 5, the average normalized GAGs from the obese group (BMI > 30 kg/m2) was > 4-fold higher than the average normalized GAGs in the non-obese group (BMI < 30 kg/m2). The 4-fold difference in normalized GAGs continued at day 9 with significance (p=0.0087) and widened at day 13, without significance. Some osteoarthritic knees had less tissue quality, therefore GAG testing was limited to earlier study days resulting in variable sample numbers for each study day.

Conclusion: The study results reveal a significant relationship between normalized GAGs and BMI in this population of osteoarthritic patients, supporting the connection between osteoarthritis and obesity previously reported. Higher patient BMI (> 30 kg/m2) may be similar to dynamic compression injuries that cause increased GAG synthesis in response to cartilage damage. In conclusion, elevated normalized GAGs in obese patients’ chondrocytes suggests increased cartilage damage.