ABSTRACT. Osteoarthritis (OA) is the most common musculoskeletal disease, affecting millions of individuals worldwide. New treatment approaches require an understanding of the pathophysiology of OA and its biomechanical, inflammatory, genetic, and environmental risk factors. The purpose of animal models of OA is to reproduce the pattern and progression of degenerative damage in a controlled fashion, so that opportunities to monitor and modulate symptoms and disease progression can be identified and new therapies developed. This review discusses the features, strengths, and weaknesses of the common animal models of OA; considerations to be taken when choosing a method for experimental induction of joint degeneration; and the challenges of measuring of OA progression and symptoms in these models.

Objective. To investigate whether cartilage degeneration is prevented or minimized following intraarticular injections of lubricin derived from human synoviocytes in culture, recombinant human PRG4 (rhPRG4), or human synovial fluid (SF) in a rat model of anterior cruciate ligament (ACL) injury.Methods. Unilateral ACL transection (ACLT) was performed in Lewis rats (n ‫؍‬ 45). Nine animals were left untreated. The remaining rats were given intraarticular injections (50 l/injection) of either phosphate buffered saline (PBS) (n ‫؍‬ 9), human synoviocyte lubricin (200 g/ml; n ‫؍‬ 9), rhPRG4 (200 g/ml; n ‫؍‬ 9), or human SF lubricin (200 g/ml; n ‫؍‬ 9) twice weekly beginning on day 7 after injury. Joints were harvested on day 32 after injury. Histologic analysis was performed using Safranin O-fast green staining, and articular cartilage degeneration was graded using the Osteoarthritis Research Society International (OARSI)-modified Mankin criteria. Histologic specimens were immunoprobed for lubricin and sulfated glycosaminoglycans. A 24-hour urine collection was performed on days 17 and 29 postinjury, and urinary C-terminal telopeptide of type II collagen (CTX-II) levels were measured.Results. Treatment with human synoviocyte lubricin resulted in significantly lower OARSI scores for cartilage degeneration compared with no treatment or PBS treatment (P < 0.05). Increased immunostaining for lubricin in the superficial zone chondrocytes and on the surface of cartilage was observed in lubricin-treated, but not untreated or PBS-treated, joints. On day 17, urinary CTX-II levels in human synoviocyte lubricinand human SF lubricin-treated animals were significantly lower than those in untreated animals (P ‫؍‬ 0.005 and P ‫؍‬ 0.002, respectively) and in PBS-treated animals (P ‫؍‬ 0.002 and P < 0.001, respectively).Conclusion. After treatment with any of the 3 types of lubricin evaluated in this study, a reduction in cartilage damage following ACLT was evident, combined with a reduction in type II collagen degradation. Our findings indicate that intraarticular lubricin injection following an ACL injury may be beneficial in retarding the degeneration of cartilage and the development of posttraumatic OA.

The coefficient of friction (COF) of articular cartilage is thought to increase with osteoarthritis (OA) progression, and this increase may occur due to a decrease in lubricin concentration. The objectives of this study were to measure the COF of guinea pig tibiofemoral joints with different stages of OA and to establish relationships between COF, lubricin concentrations in synovial fluid, and degradation status using the Hartley guinea pig model. Both hind limbs from 24 animals were harvested: seven 3-month-old (no OA), seven 12-month-old (mild OA), and 10 that were euthanized at 12 months of age after undergoing unilateral ACL transection at 3 months of age (moderate OA). Contralateral knees served as age-matched controls. COFs of the tibiofemoral joints were measured using a pendulum apparatus. Synovial fluid lavages were analyzed to determine the concentration and integrity of lubricin using ELISA and Western blot, and the overall articular cartilage status was evaluated by histology. The results showed that the mean COF in the ACL-deficient knees was significantly greater than that of the no OA (p < 0.01) and mild OA knees (p < 0.01). Lubricin concentrations in the ACL-deficient knees were significantly lower than that in both of the other groups (p < 0.01). No significant differences in COF or lubricin concentration were found between the no OA and mild OA knees. Histology verified the extent of cartilage damage in each group. ß

Background-Lubricin and hyaluronic acid lubricate articular cartilage and prevent wear. Because lubricin loss occurs following ACL injury, intra-articular lubricin injections may reduce cartilage damage in the ACL deficient knee.

ABSTRACT:The objective was to compare biomarkers of articular cartilage metabolism in synovial fluid from Hartley guinea pig knees, with and without anterior cruciate ligament transection (ACLT), to establish whether detectable differences in biomarker levels exist between primary and secondary osteoarthritis (OA). Synovial fluid lavages and knees were obtained from 3-month (control group) and 12-month (primary OA group) animals. Another group of animals (posttraumatic OA group) underwent unilateral ACLT at 3 months, and samples were obtained 9 months postsurgery. Synovial fluid concentrations of stromal cell-derived-factor (SDF-1), collagen fragments (C2C), proteoglycan (GAG), lubricin, matrix metalloproteinase-13 (MMP-13), and Interleukin-1 (IL-1b) were evaluated. Cartilage damage was assessed via histology. The highest concentrations of C2C and SDF-1 in synovial fluid were found in the posttraumatic OA group, moderate concentrations were found in the primary OA group, and low concentrations in the control group. GAG release in synovial fluid was similar to C2C and SDF-1. The lubricin concentrations were significantly lower in ACLT joints than either the control or 12-month primary OA groups, but not between the control and primary OA groups. Higher levels of MMP-13 and IL-1b were detected in the joints of the posttraumatic OA group as compared to the control or primary OA groups. Histology revealed greatest OA damage in the posttraumatic OA group, followed by moderate and minimal damage in primary OA and control groups, respectively. This study indicates that the biomarkers and progression of OA may differ in the Hartley guinea pig models with and without posttraumatic OA. ß