Regional differences in prostaglandin E2 and nitric oxide production in the knee meniscus in response to dynamic compression

Abstract

Injury or loss of the knee meniscus is associated with altered joint stresses that lead to progressive joint degeneration. The goal of this study was to determine if dynamic mechanical compression influences the production of inflammatory mediators by meniscal cells. Dynamic compression increased prostaglandin E2 (PGE(2)) and nitric oxide (NO) production over a range of stress magnitudes (0.0125-0.5 MPa) in a manner that depended on stress magnitude and zone of tissue origin. Inner zone explants showed greater increases in PGE(2) and NO production as compared to outer zone explants. Meniscal tissue expressed NOS2 and NOS3 protein, but not NOS1. Mechanically induced NO production was blocked by NOS inhibitors, and the non-selective NOS inhibitor L-NMMA augmented PGE(2) production in the outer zone only. These findings suggest that the meniscus may serve as an intra-articular source of pro-inflammatory mediators, and that alterations in the magnitude or distribution of joint loading could significantly influence the production of these mediators in vivo.

In vivo cartilage strain increases following medial meniscal tear and correlates with synovial fluid matrix metalloproteinase activity

“…Furthermore, the knee state and type of exercise impact alterations in COMP levels, as in healthy knees serum COMP levels correlate with cartilage volume changes after drop landing but not after running (Niehoff et al, 2011). PGE2 is also increased in osteoarthritic synovial fluid (Nishimura et al, 2002) and is mechanically regulated in cartilage, as well as meniscus (Fermor et al, 2002; Hennerbichler et al, 2007; Waters et al, 2014). Finally, a trend towards increased C2C was reported at 30 days following a single 8 MPa stress on cartilage explants (Barr et al, 2014).…”

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

“…have shown that the application of 0.05 MPa or 0.1 MPa of dynamic compressive stress to porcine meniscal explants resulted in final measured strains of 10% or 20%, respectively49. At higher magnitudes of loading, meniscal explants appear to exhibit a pro-inflammatory response, characterized by increased production of NOS2 and prostaglandin E240. Thus, to examine a range of physiologic and hyper-physiologic conditions, we assessed the effects of dynamic compression at strains ranging from 0 – 26% at a frequency of 1 Hz.…”

“…Furthermore, porcine meniscal explants subjected to 0 – 20% strain have shown no change in NO release41. However, other studies have shown conflicting results from decreased NO release by 15% strain of chondrocyte-agarose constructs59, 60 to increased NO production by porcine meniscal explants subjected to dynamic compressive stresses of 0.0125 – 0.5 MPa at 1 Hz for 24 hours39, 40. These differences are likely attributable to the different model systems and magnitudes of the applied stress or strain, particularly the overall duration of loading.…”

“…Meniscal explants subjected to static compression showed decreased expression of type I and II collagen37, increased MMP-1 expression37, and decreased biosynthetic activity, as measured by 35 S-sulfate and 3 H-proline incorporation38. Dynamic mechanical compression increases proteoglycan and total protein synthesis22 and NO and PGE 2 production by meniscal explants39, 40. Additionally 20% compressive strain of porcine explants caused increased expression of the following catabolic mediators: inducible nitric oxide synthase (NOS2), IL-1α, MMP-1, MMP-3, MMP-13, and a disintegrin and metalloproteinase with thrombospondin 4 (ADAMTS-4)41, 42.…”

Dynamic compressive loading of image-guided tissue engineered meniscal constructs

“…Several studies have utilized dynamic compression to characterize the mechanical properties and behavior of meniscal explants (Bursac et al, 2009;Chia and Hull, 2008;Wilson et al, 2009) as well as examine gene expression (Upton et al, 2003) and protein synthesis (Fink et al, 2001;Hennerbichler et al, 2007;Shin et al, 2003) of meniscal fibrochondrocytes in their native environment. While it has been observed that dynamic compression can enhance extracellular matrix (ECM) production (Zielinska et al, 2009) as well as increase the gene expression for collagenase and matrix metalloproteinases (MMPs) (Upton et al, 2003), it should be noted that the native tissue environment can greatly differ from other tissue engineering studies depending on the biomaterial used.…”