Meniscal tissue explants response depends on level of dynamic compressive strain

SummaryObjectiveFollowing partial meniscectomy, the remaining meniscus is exposed to an altered loading environment. In vitro 20% dynamic compressive strains on meniscal tissue explants has been shown to lead to an increase in release of glycosaminoglycans from the tissue and increased expression of interleukin-1α (IL-1α). The goal of this study was to determine if compressive loading which induces endogenously expressed IL-1 results in downstream changes in gene expression of anabolic and catabolic molecules in meniscal tissue, such as MMP expression.MethodRelative changes in gene expression of MMP-1, MMP-3, MMP-9, MMP-13, A Disintegrin and Metalloproteinase with ThromboSpondin 4 (ADAMTS4), ADAMTS5, TNFα, TGFβ, COX-2, Type I collagen (COL-1) and aggrecan and subsequent changes in the concentration of prostaglandin E2 released by meniscal tissue in response to varying levels of dynamic compression (0%, 10%, and 20%) were measured. Porcine meniscal explants were dynamically compressed for 2h at 1Hz.Results20% dynamic compressive strains upregulated MMP-1, MMP-3, MMP-13 and ADAMTS4 compared to no dynamic loading. Aggrecan, COX-2, and ADAMTS5 gene expression were upregulated under 10% strain compared to no dynamic loading while COL-1, TIMP-1, and TGFβ gene expression were not dependent on the magnitude of loading.ConclusionThis data suggests that changes in mechanical loading of the knee joint meniscus from 10% to 20% dynamic strain can increase the catabolic activity of the meniscus

IL-1 and iNOS gene expression and NO synthesis in the superior region of meniscal explants are dependent on the magnitude of compressive strains

OBJECTIVE: Partial meniscectomy is known to cause osteoarthritis (OA) of the underlying cartilage as well as alter the load on the remaining meniscus. Removal of 30-60% of the medial meniscus increases compressive strains from a maximum of approximately 10% to almost 20%. The goal of this study is to determine if meniscal cells produce catabolic molecules in response to the altered loading that results from a partial meniscectomy. METHOD: Relative changes in gene expression of interleukin-1 (IL-1), inducible nitric oxide synthase (iNOS) and subsequent changes in the concentration of nitric oxide (NO) released by meniscal tissue in response to compression were measured. Porcine meniscal explants were dynamically compressed for 2 h at 1 Hz to simulate physiological stimulation at either 10% strain or 0.05 MPa stress. Additional explants were pathologically stimulated to either 0% strain, 20% strain or, 0.1 MPa stress. RESULTS: iNOS and IL-1 gene expression and NO release into the surrounding media were increased at 20% compressive strain compared to other conditions. Pathological unloading (0% compressive strain) of meniscal explants did not significantly change expression of IL-1 or iNOS genes, but did result in an increased amount of NO released compared to physiological strain of 10%. CONCLUSION: These data suggest that meniscectomies which reduce the surface area of the meniscus by 30-60% will increase the catabolic activity of the meniscus which may contribute to the progression of OA

Deleterious effects of osteoarthritis on the structure and function of the meniscal enthesis

SummaryObjectiveThe ability of menisci to prevent osteoarthritis (OA) is dependent on the integrity of the complex meniscal entheses, the attachments of the menisci to the underlying subchondral bone (SB). The goal of this study was to determine mechanical and structural changes in meniscal entheses after the onset of OA.DesignHealthy and osteoarthritic meniscal entheses were evaluated for changes in histomorphological characteristics, mineralization, and mechanical properties. Glycosaminoglycans (GAG) and calcium in the insertion were evaluated with histological staining techniques. The extent of calcium deposition was assessed and tidemark (TM) integrity was quantified. Changes in the mineralized zone of the insertion were examined using micro-computed tomography (μCT) to determine bone mineral density, cortical zone thickness, and mineralization gradient. Mechanical properties of the entheses were measured using nano-indentation techniques to obtain material properties based on viscoelastic analysis.ResultsGAG thickness in the calcified fibrocartilage (CFC) zone and calcium content were significantly greater in osteoarthritic anterior meniscal entheses. TM integrity was significantly decreased in OA tissue, particularly in the medial anterior (MA) enthesis. The mineralized zone of osteoarthritic meniscal entheses was significantly thicker than in healthy entheses and showed decreased bone mineral density. Fitting of mineralization data to a sigmoidal Gompertz function revealed a lower rate of increase in mineralization in osteoarthritic tissue. Analysis of viscoelastic mechanical properties revealed increased compliance in osteoarthritic tissue.ConclusionsThese data suggest that significant changes occur at meniscal enthesis sites with the onset of OA. Mechanical and structural changes in meniscal entheses may contribute to meniscal extrusion, which has been shown to increase the progression of OA