Osteophytes are a typical radiographic finding during osteoarthritis (OA). Osteophytes are thought to form in response to joint instability, however the time course of osteophyte formation and joint stabilization following joint injury is not well understood. In this study, we investigated the time course of osteophyte formation and joint function following non-invasive knee injury in mice. We hypothesized that initial joint instability following knee injury would initiate osteophyte formation, which would in turn restabilize the joint and reduce range of motion (ROM). Mice were subjected to non-invasive anterior cruciate ligament (ACL) rupture. Anterior-posterior (AP) joint laxity, ROM, and chondro/osteophyte formation were measured immediately after injury, and 2, 4, 6, and 8 weeks post-injury. Chondrophyte areas at each time point were measured with histology, while mineralized osteophyte volume was determined using micro-computed tomography. Immediately after ACL rupture, AP joint laxity was increased 2-fold, while ROM was increased 11.7%. Chondrophytes appeared by 2 weeks post-injury, corresponding with a decrease in AP joint laxity and ROM. By 8 weeks post-injury, considerable osteophyte formation was observed around the joint, AP joint laxity returned to control levels, and joint ROM decreased to 61% of control values. These data support a role for chondro/osteophytes in joint restabilization after injury, and provide crucial insight into the time course and pathology of joint degeneration during OA development in the mouse.

Although histopathological confirmation (lung biopsy) is considered the gold standard for EMPF diagnosis, results of qPCR testing of BALF or a combination of whole blood and nasal secretions should be regarded as clinically useful in support of this diagnosis. The latter testing may be relevant when dealing with horses in respiratory distress, for which invasive procedures such as BALF collection or lung biopsies may be detrimental to their health.

Recently, autophagy-related proteins were shown to regulate osteoclast mediated bone resorption, a critical process in autoimmune diseases such as rheumatoid arthritis. However, the role of autophagy-linked FYVE containing protein, WDFY3, in osteoclast biology remains elusive. WDFY3 is a master regulator in selective autophagy for clearing ubiquitinated protein aggregates and has been linked with rheumatoid arthritis. Herein, we used a series of WDFY3 transgenic mice (Wdfy3lacZ and Wdfy3loxP) to investigate the function of WDFY3 in osteoclast development and function. Our data demonstrate that WDFY3 is highly expressed at the growth plate of neonatal mice and is expressed in osteoclasts in vitro cultures. Osteoclasts derived from WDFY3 conditional knockout mice (Wdfy3loxP/loxP-LysM-Cre+) demonstrated increased osteoclast differentiation as evidenced by higher number and enlarged size of TRAP+ multinucleated cells. Western blot analysis also revealed up-regulation of TRAF6 and an increase in RANKL-induced NF-κB signaling in WDFY3-deficient bone marrow-derived macrophages compared to wild type cultures. Consistent with these observations WDFY3-deficient cells also demonstrated an increase in osteoclast-related genes Ctsk, Acp5, Mmp9 and an increase of dentine resorption in in vitro assays. Importantly, in vivo RANKL gene transfer exacerbated bone loss in WDFY3 conditional knockout mice, as evidenced by elevated serum TRAP, CTX-I and micro-CT analysis of distal femurs compared to wild type littermates. Taken together, our data highlight a novel role for WDFY3 in osteoclast development and function, which can be exploited for the treatment of musculoskeletal diseases.

Lumbar vertebral fractures occur in racehorses with pre-existing pathology at the L5-L6 vertebral junction that is likely predisposes horses to catastrophic fracture. Knowledge of these findings should encourage assessment of the lumbar vertebrae, therefore increasing detection of mild vertebral injuries and preventing catastrophic racehorse and associated jockey injuries.