Dynamic loading enhances integrative meniscal repair in the presence of interleukin-1

Abstract

Objective Meniscal tears are a common knee injury and increased levels of interleukin-1 (IL-1) have been measured in injured and degenerated joints. Studies have shown that IL-1 decreases the shear strength, cell accumulation, and tissue formation in meniscal repair interfaces. While mechanical stress and IL-1 modulate meniscal biosynthesis and degradation, the effects of dynamic loading on meniscal repair are unknown. The purpose of this study was to determine the effects of mechanical compression on meniscal repair under normal and inflammatory conditions. Experimental Design Explants were harvested from porcine medial menisci. To simulate a full-thickness defect, a central core was removed and reinserted. Explants were loaded for 4 hours/day at 1Hz and 0 – 26% strain for 14 days in the presence of 0 or 100pg/mL of IL-1. Media were assessed for matrix metalloproteinase (MMP) activity, aggrecanase activity, sulfated glycosaminoglycan (S-GAG) release, and nitric oxide (NO) production. After 14 days, biomechanical testing and histological analyses were performed. Results IL-1 increased MMP activity, S-GAG release, and NO production, while decreasing the shear strength and tissue repair in the interface. Dynamic loading antagonized IL-1-mediated inhibition of repair at all strain amplitudes. Neither IL-1 treatment nor strain altered aggrecanase activity. Additionally, strain alone did not alter meniscal healing, except at the highest strain magnitude (26%), a level that enhanced the strength of repair. Conclusions Dynamic loading blocked the catabolic effects of IL-1 on meniscal repair, suggesting that joint loading through physical therapy may be beneficial in promoting healing of meniscal lesions under inflammatory conditions.

Reduced response of human meniscal cells to Osteogenic Protein 1 during osteoarthritis and pro-inflammatory stimulation

“…Importantly, the reduced ability of OP1 to stimulate extracellular matrix gene expression and to reduce MMP expression in meniscus cells obtained from end-stage OA knee joints suggests that factors associated with OA inhibit the response to OP1. We found evidence that these could include IL1α, IL1β, and FnF which have been found to be present in torn meniscus and/or OA joint fluid [26, 27]. We also confirmed previous work [13] that unlike the meniscus, OA chondrocytes do not appear to become unresponsive to OP1 suggesting differences in the regulation of OP1 signaling between these two joint tissues.…”

Chronic changes in the articular cartilage and meniscus following traumatic impact to the lapine knee

“…Furthermore, a previous canine ACL transection study (Adams et al, 1983) documented initial decreases in meniscal GAG at 1 week post injury with levels returning to normal or above normal after 15–18 months. This initial decrease in GAG could be due to an inflammatory response, as numerous studies (Lemke et al, 2010; McNulty et al, 2010) have demonstrated GAG degradation under inflammatory conditions. We were limited in our assessment of GAG changes, as they may be temporal and this study is presenting results from a single time point of 12 weeks.…”

TRPV4-mediated mechanotransduction regulates the metabolic response of chondrocytes to dynamic loading

“…Dynamic compressive loading was performed as previously described (60). Briefly, a closed-loop displacement controlled bioreactor with 24 individual polyacetal pistons connected to a linear stage driven by a stepper motor was used to deliver a 10% peak-to-peak sinusoidal strain (7% offset) at 1 Hz for 3 h/d.…”