Certain types of joint injuries, common in athletes, are known to have a high association with the development of osteoarthritis (OA). Post-traumatic osteoarthritis (PTOA) is especially debilitating due to its earlier onset than traditional OA, and its predisposition to affect a younger and more active population. Five common athletic injuries have been demonstrated to be risk factors for the development of OA. These include ACL rupture, meniscus tear, glenohumeral instability, patellar dislocation, and ankle instability. Though the mechanisms responsible for the development of PTOA are not entirely clear, certain kinematic, biologic, and mechanical factors have been implicated. In addition, there has been an increased emphasis on development of new methods to detect early OA changes in patients with known risk factors, as early intervention may prevent the development of end-stage OA. New imaging modalities as well as the identification of specific biomarkers may allow earlier detection. Though these developments hold promise, it is not entirely known what steps we can take today to prevent the future development of OA, even with early detection. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:397-405, 2017.

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ABSTRACT:The structure and composition of the native enthesis is not recapitulated following tendon-to-bone repair. Indian Hedgehog (IHH) signaling has recently been shown to be important in enthesis development in a mouse model but no studies have evaluated IHH signaling in a healing model. Fourteen adult male rats underwent ACL reconstruction using a flexor tendon graft. Rats were assigned to two groups based on whether or not they received 0N or 10N of pre-tension of the graft. Specimens were evaluated at 3 and 6 weeks post-operatively using immunohistochemistry for three different protein markers of IHH signaling. Quantitative analysis of staining area and intensity using custom software demonstrated that IHH signaling was active in interface tissue formed at the healing tendon-bone interface. We also found increased staining area and intensity of IHH signaling proteins at 3 weeks in animals that received a pre-tensioned tendon graft. No significant differences were seen between the 3-week and 6-week time points. Our data suggests that the IHH signaling pathway is active during the tendon-bone healing process and appears to be mechanosensitive, as pretensioning of the graft at the time of surgery resulted in increased IHH signaling at three weeks. ß

Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of neovascular age-related macular degeneration and diabetic retinopathy. Bevacizumab, an anti-VEGF monoclonal antibody, is efficacious for these disorders, but requires monthly intravitreal administration, with associated discomfort, cost, and adverse event risk. We hypothesized that a single intravitreal administration of adeno-associated virus (AAV) vector expressing bevacizumab would result in persistent eye expression of bevacizumab and suppress VEGF-induced retinal neovascularization. We constructed an AAV rhesus serotype rh.10 vector to deliver bevacizumab (AAVrh.10BevMab) and assessed its ability to suppress neovascularization in transgenic mice overexpressing human VEGF165 in photoreceptors. Intravitreal AAVrh.10BevMab directed long-term bevacizumab expression in the retinal pigmented epithelium. Treated homozygous mice had reduced levels of neovascularization, with 90±4% reduction 168 days following treatment. Thus, a single administration of AAVrh.10BevMab provides long-term suppression of neovascularization without the costs and risks associated with the multiple administrations required for the current conventional bevacizumab monoclonal drug delivery.

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