LOXL2 in anabolic response to chondrodysplasia mice progressive TMJ and knee osteoarthritis
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Osteoarthritis (OA) is a degenerative joint disease that affects an estimated 9.6 % of men and 18 % of women over 60 years of age. However, there is no chondroprotective agent that is approved for clinical application. We showed that LOXL2 is elevated in the regenerative response during fracture healing in mice and has a critical role in chondrogenic differentiation. Indeed, LOXL2 is an anabolic effector that attenuates pro-inflammatory signaling in OA cartilage of the TMJ and knee joint, induces chondroprotective and regenerative responses. The goal of the present study was to evaluate if LOXL2 adenovirus in vivo promotes protective and anabolic responses in the knee and TMJ-OA cartilage. We employed (Cho/+) OA mouse model to assess knee and TMJ-OA, which is a genetic model that develops progressive TMJ-OA due to a mutation in the Col11a1 gene. Intraperitoneal injection every 2 weeks of Adv-RFP-LOXL2 in four-month-old Cho/+ male and female mice for 16 weeks upregulated Sox9, aggrecan (Acan) and other anabolic genes in the knee and TMJ. Next, to evaluate if LOXL2 expression occurred in degenerative lesions in human clinical TMJ-OA, immunofluorescence and confocal image analysis were performed. LOXL2 has the potential to induce anabolic gene expression in the progressive knee and TMJ-OA mouse model. We showed for the first time that LOXL2-related functions could be useful for anabolic therapies for Cho/+ mice progressive knee and TMJ-OA. Thus, these data show that LOXL2 could have clinical translational applications in the future for OA-related anabolic therapies.