Osteoarthritis (OA) is a costly and debilitating condition that is typically not diagnosed early enough to prevent progression of disease. The purpose of this study was to evaluate synovial fluid from knees with and without OA for potential markers of joint inflammation and degradation and to correlate these findings with radiographic severity of disease. With Institutional Review Board approval, synovial fluid samples were collected before the patient undergoing total knee arthroplasty. Control knees (n = 3) were patients younger than 30 years of age with no history of anterior cruciate ligament, posterior cruciate ligament, or meniscal injury, and no surgical history for either knee. Weight-bearing, anterior-posterior radiographic views were used to determine radiographic OA severity using the modified Kellgren and Lawrence scale. Synovial fluid samples from 18 patients (21 knees) were analyzed using a multiplex assay. Matrix metalloproteinase (MMP)-1 (p < 0.001), interleukin (IL)-6 (p < 0.013), IL-8 (p < 0.024), and Chemokine (C-C motif) ligand 5 (CCL5) (p < 0.006) were significantly higher in the synovial fluid of OA patients compared with normal patients. The radiographic score was significantly higher in patients with OA compared with normal knees (p < 0.002). MMP-1 had a moderate positive correlation with MMP-2, IL-6, IL-8, and CCL5. IL-6 had a strong positive correlation with IL-8 and a moderate positive correlation with MMP-2. Monocyte chemotactic protein 1 had a moderate positive correlation with IL-6 and a strong positive correlation with IL-8. Radiographic scores had a strong positive correlation with IL-6 and IL-8 and a moderate positive correlation with MCP-1. These data provide novel and clinically relevant information for the investigation of synovial fluid biomarkers for knee OA.

Translational models of posttraumatic osteoarthritis (PTOA) that accurately represent clinical pathology need to be developed. This study assessed a novel canine model for PTOA using impact injury. Impacts were delivered to the medial femoral condyle of dogs using a custom-designed impactor at 20, 40, or 60 MPa. Functional assessments and magnetic resonance imaging (MRI) were performed at 2 and 12 weeks, and arthroscopic and histologic assessments were performed at 12 weeks after injury. At 2 and 12 weeks, dogs had observable lameness, knee pain, effusion, loss in range of motion (ROM) and dysfunction in both hindlimbs with severity correlated strongly (r > 0.77) to impact level. At 12 weeks, function, pain, effusion, and ROM were significantly (p < 0.049) worse in knees impacted at 40 and 60 MPa compared with 20 MPa. MRI showed consistent cartilage and subchondral bone marrow lesions, and arthroscopy revealed synovitis and cartilage destruction in impacted knees, with increased severity for 40 and 60 MPa impacts. Histopathology was significantly (p = 0.049) more severe in 40 and 60 MPa and strongly correlated (r = 0.93) to impact level. This novel translational model appears to be valid for investigation of PTOA, including determination of temporal mechanisms of disease and preclinical testing for preventative and therapeutic strategies.

The knee is a fascinating yet complex joint. Researchers and clinicians agree that the joint is an organ comprised of highly specialized intrinsic and extrinsic tissues contributing to both health and disease. Key to the function and movement of the knee are the menisci, exquisite fibrocartilage structures that are critical structures for maintaining biological and biomechanical integrity of the joint. The biological/physiological functions of the menisci must be understood at the tissue, cellular and even molecular levels in order to determine clinically relevant methods for assessing it and influencing it. By investigating normal and pathological functions at the basic science level, we can begin to translate data to patients. The objective of this article is to provide an overview of this translational pathway so that progression toward improved diagnostic, preventative, and therapeutic strategies can be effectively pursued. We have thoroughly examined the pathobiological, biomarker, and imaging aspects of meniscus research. This translational approach can be effective toward optimal diagnosis, prevention, and treatment for the millions of patients who suffer from meniscal disorders each year.

Meniscal pathology is an extremely prevalent problem, which inevitably leads to osteoarthritis and associated pain, swelling, and disability. Relatively little data are available regarding the molecular, biochemical, and histologic aspects of meniscal disease. This study characterizes meniscal pathology in the presence of symptomatic osteoarthritis and correlates clinical and basic science data in an attempt to delineate clinically relevant mechanisms of disease. Twenty-seven knees from 23 patients who underwent total knee arthroplasty comprised the affected group and 6 aged nonsymptomatic knees were used as controls. All meniscal tissues were harvested and subjectively scored for gross and histologic pathology. Biochemical analyses were performed to determine glycosaminoglycan (GAG) content, collagen (hydroxyproline) content, and water content. Real-time polymerase chain reaction analysis was conducted for genes involved in synthesis (collagens [col] 1, 2, 3, and 6), degradation (matrix metalloproteinases [MMP-1, -2, -3, -13]), and angiogenesis (vascular endothelial growth factor). Weight-bearing, anterior-posterior radiographic views were used to determine joint space measurements for lateral and medial compartments, and were subjectively scored for osteoarthritic changes. Data were compared for statistically significant differences and to determine the presence and strength of correlations among variables assessed. Affected menisci had significantly higher gross and histologic pathology scores compared with control menisci. Affected menisci had significantly higher water, proteoglycan, and collagen content compared with control menisci. Col 1, 3, and 6 gene expression levels for the affected group were significantly increased compared with controls. MMP-13 expression was significantly increased for the affected group. MMP-2 and -3 expression levels were significantly lower in the affected group compared with controls. The affected group had significantly more joint space narrowing and higher radiographic scores for medial compared with lateral compartments. Several strong and moderately strong correlations were present between variables. These data suggest that in vitro measures of meniscal pathology have potential value for understanding disease mechanisms and predicting clinical disease.

Musculoskeletal injuries are a common problem in orthopedic practice. Given the long-term consequences of unaddressed cartilage and meniscal pathology, a number of treatments have been attempted to stimulate repair or to replace the injured tissue. Despite advances in orthopedic surgery, effective treatments for cartilage and meniscus injuries remain a significant clinical challenge. Tissue engineering is a developing field that aims to regenerate injured tissues with a combination of cells, scaffolds, and signals. Many natural and synthetic scaffold materials have been developed and tested for the repair and restoration of a number of musculoskeletal tissues. Among these, biological scaffolds derived from cell and tissue-derived extracellular matrix (ECM) have shown great promise in tissue engineering given the critical role of the ECM for maintaining the biological and biomechanical properties, structure, and function of native tissues. This review article presents emerging applications for tissue-derived ECM scaffolds in cartilage and meniscus repair. We examine normal ECM composition and the current and future methods for potential treatment of articular cartilage and meniscal defects with decellularized scaffolds.