In Vivo Effect of Opticin Deficiency in a Surgically Induced Mouse Model of Osteoarthritis

Aina Farran¹, Gladys Valverde-Franco², Laura Tio³, Bertrand Lussier⁴, Hassan Fahmi², Jean-Pierre Pelletier², Paul Bishop⁵, Jordi Monfort⁶ and Johanne Martel-Pelletier², ¹Osteoarthritis Research Unit (CRCHUM), Montreal; Inflammation and Cartilage Cellular Research Group, IMIM (Hospital del Mar Research Unit) Rheumatology Department, Parc de Salut Mar, Hospital del Mar, Barcelona, Barcelona, Spain, ²Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Montreal, QC, Canada, ³Inflammation and Cartilage Cellular Research Group, IMIM (Hospital del Mar Research Unit) Rheumatology Department, Parc de Salut Mar, Hospital del Mar, Barcelona, Spain, ⁴Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM); Faculty of Veterinary Medicine, Clinical Sciences, University of Montreal, Sainte-Hyacinthe, QC, Canada, ⁵Manchester Royal Eye Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre; School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom, ⁶Inflammation and Cartilage Cellular Research Group, IMIM (Hospital del Mar Research Unit) Rheumatology Department, Parc de Salut Mar; Rheumatology Department, Hospital del Mar, Barcelona, Spain

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: mouse model and osteoarthritis

Session Information

Date: Sunday, November 5, 2017

Title: Biology and Pathology of Bone and Joint Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Opticin (OPTC) is a small leucine-rich proteoglycan (SLRP) that has been previously demonstrated to be produced and degraded in osteoarthritic (OA) human cartilage. Here, we further investigated the in vivo effect of OPTC deficiency in OA cartilage.

Methods: OA was induced in 10-week-old Optc^-/- (knock-out) and Optc^+/+ (wild type) mice by destabilization of the medial meniscus (DMM). Ten weeks post-surgery, cartilage was processed for histology, and immunohistochemistry. SLRP expression was determined in non-operated mouse cartilage at day 3 (P03) and 10 weeks of age. Collagen ultrastructure was analyzed by transmission electron microscopy in 10-week-old non-operated mouse cartilage.

Results: OA Optc^-/- mice demonstrated significant protection against cartilage degradation. Data revealed that in non-operated Optc^-/- mouse cartilage, the SLRPs lumican and epiphycan were significantly up-regulated at P03 (p≤0.010) and 10 weeks old (p≤0.007), and fibromodulin down-regulated at 10 weeks of age (p≤0.001). Immunohistochemistry of OA mice showed a similar pattern. In OA Optc^-/- mouse cartilage, markers of cartilage degradation and complement factors C5b-9 and CCL2 were all down-regulated (p≤0.050). In Optc^-/- mouse cartilage, collagen fibers were thinner and better organized (p=0.038) than in OA Optc^+/+ mouse cartilage.

Conclusion: This work demonstrates a protective effect of OPTC deficiency during OA, resulting from an overexpression of lumican and epiphycan, known to bind and protect collagen fibers, and a decrease in fibromodulin, contributing to a reduction in the complement activation/inflammatory process. This work suggests that the evaluation of the composition of the different SLRPs in OA cartilage could be applied as a new tool for OA prognosis classification.

Disclosure: A. Farran, None; G. Valverde-Franco, None; L. Tio, None; B. Lussier, None; H. Fahmi, None; J. P. Pelletier, None; P. Bishop, None; J. Monfort, None; J. Martel-Pelletier, None.

To cite this abstract in AMA style:

Farran A, Valverde-Franco G, Tio L, Lussier B, Fahmi H, Pelletier JP, Bishop P, Monfort J, Martel-Pelletier J. In Vivo Effect of Opticin Deficiency in a Surgically Induced Mouse Model of Osteoarthritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/in-vivo-effect-of-opticin-deficiency-in-a-surgically-induced-mouse-model-of-osteoarthritis/. Accessed .

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