s / Osteoarthritis and Cartilage 23 (2015) A82eA416 A284 Purpose: The infrapatellar fat pad (IPFP) is commonly resected during knee joint arthroplasty. This longitudinal study examined the associations between the maximum cross-sectional area (CSA) of the IPFP and knee cartilage volume and pain in adults without knee osteoarthritis (OA). Methods: 297 adults without baseline knee pain or a diagnosis of knee OA had MRI performed at baseline and follow-up (n 1⁄4 271). IPFP maximal CSA and tibial cartilage volume were measured from MRI. Body composition was performed at baseline using bio-impedance. Knee pain was assessed at follow-up using the Western Ontario and McMaster University Osteoarthritis Index (WOMAC). Results: A larger IPFP at baselinewas associatedwith reduced knee pain at follow-up (OR 0.5, 95% CI: 0.3 to 0.9, p 1⁄4 0.02) and lateral tibial cartilage volume loss (b: -0.9% (95% CI: -1.6, -0.1%) per annum, p1⁄4 0.03). The maximal CSA of the IPFP was predominantly located in the lateral (54.2%), rather than the medial tibiofemoral compartment (1.7%). Male gender (OR 12.0, 95% CI: 6.5 to 22.0, p < 0.001) and fat free mass (OR 1.15, 95% CI 1.04 to 1.28, p 1⁄4 0.007) were both associated with a large IPFP. Conclusions: A larger IPFP predicts reduced lateral tibial cartilage volume loss and knee pain and mechanistically might function as a local shock-absorber. The lack of association between measures of adiposity and the size of the IPFP might suggest that the IPFP size is not simply a marker of systemic obesity. OA: Cartilage and Bone 446 HIGH SYSTEMIC LDL CHOLESTEROL LEVELS DURING EXPERIMENTAL OSTEOARTHRITIS LEAD TO INCREASED SYNOVIAL ACTIVATION AND ECTOPIC BONE FORMATION AT END-STAGE OSTEOARTHRITIS, WHILE EXCESSIVE LEVELS ACCELERATE DEVELOPMENT OF JOINT PATHOLOGY ALREADY AT EARLY-STAGE OF OSTEOARTHRITIS W. de Munter y, M.M. van den Bosch y, A.W. Sloetjes y, P.M. van der Kraan y, T. Vogl z, J. Roth z, W.B. van den Berg y, P.L. van Lent y. yRadboud Univ. Med. Ctr., Nijmegen, Netherlands; z Inst. of Immunology, Muenster, Germany Purpose: A relation between osteoarthritis (OA) and the metabolic syndrome has long been established. One of the characteristics of the metabolic syndrome is increased cholesterol levels. In a recent study, we showed that LDL accumulationby LDL receptordeficientmice resulted in increased ectopic bone formation during experimental osteoarthritis. In the present study we investigate OA pathology in ApoE deficient (ApoE-/-) mice with and without a cholesterol-rich diet, which is a model for extremely high systemic LDL cholesterol levels. Methods: Wild type (WT) and ApoE-/mice received a normal or cholesterol-rich diet for 54 days. At day 18, experimental OA was induced by intra-articular injection of collagenase and animals were sacrificed at day 28 and 54. Gene expression in synovium was measured by RT-PCR and joint pathology was investigated by histology. LDL levels were measured in serum and synovial wash-outs. Results: ApoE-/mice on a normal diet showed markedly higher LDL levels than WT mice (8.90 mmol/L and 0.40 mmol/L, respectively; p<0.001). While no differences between the two groups were found at the early time point (day 28), end point OA (day 54) in ApoE-/mice showed a strong increase of ectopic bone formation, mainly at the medial collateral ligament (fold increase 5.4; p<0.001) compared toWT mice. No significant differences in cartilage damage were found between the two groups; a slight increase in synovial thickening, however, was found in ApoE-/-mice (arbitrary score 1.9 versus 1.1 in WT mice; p<0.05). Furthermore, synovial gene expression of both S100A8 and S100A9 (fold increase 1.8 and 1.4, respectively; p<0.05) and S100A8/S100A9 protein levels of synovial wash-outs were increased in ApoE-/mice (fold increase 5.8; p<0.05), suggesting an activated status of synovial lining cells. In addition, we investigated whether a cholesterol-rich diet could increase joint pathology after induction of OA. The diet increased LDL levels even more in ApoE-/mice (fold increase 2.1, compared to ApoE-/mice on a normal diet; p<0.001). In both ApoE-/and WT mice on a cholesterol-rich diet, excessive bone formationwas found in the medial collateral ligament at day 54, however, no significant difference was found between the two groups. Interestingly, at the early time point (day 28; 10 days after OA induction), histological differences between the two groups were observed. Synovial thickening was four times increased (p<0.001) in ApoE-/-mice on a cholesterol-rich diet and also ectopic cartilage formation in the medial collateral ligament was strongly increased (fold increase 2.7; p<0.01) compared to WT mice on a cholesterol-rich diet. Conclusions: LDL cholesterol accumulation by ApoE deficiency or a cholesterol-rich diet results in increased synovial activation and ectopic bone formation in experimental OA. Excessive LDL levels induced by a combination of ApoE deficiency and a cholesterol-rich diet strongly elevated synovial activation and ectopic bone formation at an early stage of the disease without affecting cartilage destruction. 447 EXPERIMENTAL EVALUATION OF DISCOIDIN DOMAIN RECEPTOR 2 AS AN IDEAL TARGET FOR DEVELOPMENT OF DISEASE-MODIFYING OSTEOARTHRITIS DRUGS L. Manning, L. Xu, Y. Li. Harvard Sch. of Dental Med. and Harvard Med. Sch., Boston, MA, USA Purpose: The goal of this study is to evaluate if the complete removal of Ddr2 from the knee joint of mouse adult articular cartilage can delay progression of osteoarthritis prior to or after initiation of articular cartilage degeneration. MMP-13, which has the ability to degrade both aggrecans and type II collagen, would be an ideal target for diseasemodifying osteoarthritis drugs. However, the broad biological effects of MMP-13 restrict its application as a target enzyme of inhibitor drugs in the treatment of OA. Recent studies demonstrate that a specific amino acid sequence, from amino acid 594 to 605, on type II collagen is preferentially recognized by DDR2. The expression and subsequent activation of DDR2 were increased in human OA tissues and mouse models of OA, and this was co-localized with elevated expression of MMP-13 in degenerative articular cartilages. Conversely, reduced expression of Ddr2 in the heterozygous Ddr2 knockout condition attenuated progression of articular cartilage degeneration in mouse models of OA. Typically, DDR2 is kept inactivated by the presence of the pericellular matrix, which separates chondrocytes from type II collage in healthy articular cartilage. Once enzymes, such as a serine proteinase, high temperature requirement A1, that are capable of degrading the pericellular molecules expose chondrocytes to type II collagen, DDR2 is activated and then induces expression of MMP-13 leading the degradation of type II collage and proteoglycans resulting in joint destruction and OA. Methods: 1) By use of conditional knock out techniques with aggrecanCreERt2 mice and floxed Ddr2 mice, Ddr2 was removed from articular cartilage of knee joints in mice at 8 weeks of age via intraperitoneal injection Tamoxifen injection (2mg/10g body weight) for 5 consecutive days (Group A). Mice were subjected to destabilization of the medial meniscus (DMM) or sham surgery at 10 weeks of age. 2) An additional experimental group was subjected to DMM or sham surgery at 10 weeks of age and then Ddr2 was removed by intraperitoneal injection Tamoxifen injection 8 weeks later (Group B). 3) Knee joints fromGroups A and B mice and their corresponding controls (n1⁄47) were then collected for morphological analysis. Knee joints from mice in Group A were harvested at 8 weeks (n1⁄47) or 16 weeks (n1⁄49) post-surgery and those from Group B (n1⁄45) at 16 weeks post-surgery. 4) Histology was performed. 5) ORASI Modified Mankin Score was used to evaluate articular cartilage degeneration. 6) Statistically significant differences were determined via T-test. Results: 1) The average modified score for Group A 8 week control was 1.64 (score range 1.5-2) whereas the average modified score with Ddr2 removed was 0.64 (score range 0.5-1) [P<0.05]. 2) The averagemodified score for Group A 16 week control was 4.67 (score range 4-5) and the average modified score with Ddr2 removed was 1.27 (score range 0.5-3) [P<0.05]. 3) The average modified score for Group Bwas 1.1 (score range 0.5-2). Conclusions: Conditional removal of Ddr2 in articular cartilage attenuated articular cartilage degeneration in mature knee joints of mouse models of OA. Therefore, inhibiting activity of DDR2, may be considered in treatment of OA in mature joints in humans. 448 ASSOCIATION BETWEEN CARTILAGE DEGENERATION AND SUBCHONDRAL BONE METABOLISM IN PATIENTS WITH KNEE OSTEOARTHRITIS M. Kretzschmar yz, O. Maas z, G.B. Joseph y, D. Wild z. yUniv. of California San Francisco, San Francisco, CA, USA; zUniv. Hosp. Basel, Basel,