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ABSTRACT Joint injury causes post-traumatic osteoarthritis (PTOA). About ∼50% of patients rupturing their anterior cruciate ligament (ACL) will develop PTOA within 1-2 decades of the injury, yet the mechanisms responsible for the development of PTOA after joint injury are not well understood. In this study, we examined whole joint gene expression by RNA sequencing (RNAseq) at 1 day, 1-, 6-, and 12 weeks post injury, in a non-invasive tibial compression (TC) overload mouse model of PTOA that mimics ACL rupture in humans. We identified 1446 genes differentially regulated between injured and contralateral joints. This includes known regulators of osteoarthritis such as MMP3, FN1, and COMP, and several new genes including Suco, Sorcs2, and Medag. We also identified 18 long noncoding RNAs that are differentially expressed in the injured joints. By comparing our data to gene expression data generated using the surgical destabilization of the medial meniscus (DMM) PTOA model, we identified several common genes and shared mechanisms. Our study highlights several differences between these two models and suggests that the TC model may be a more rapidly progressing model of PTOA. This study provides the first account of gene expression changes associated with PTOA development and progression in a TC model. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 35:474-485, 2017. [ABSTRACT FROM AUTHOR]

Fracture healing involves rapid stem and progenitor cell migration, homing, and differentiation. SDF-1 (CXCL12) is considered a master regulator of CXCR4-positive stem and progenitor cell trafficking to sites of ischemic (hypoxic) injury and regulates their subsequent differentiation into mature reparative cells. In this study, we investigated the role of SDF-1/CXCR4 signaling in fracture healing where vascular disruption results in hypoxia and SDF-1 expression. Mice were injected with AMD3100, a CXCR4 antagonist, or vehicle twice daily until euthanasia with the intent to impair stem cell homing to the fracture site and/or their differentiation. Fracture healing was evaluated using micro-computed tomography, histology, quantitative PCR, and mechanical testing. AMD3100 administration resulted in a significantly reduced hyaline cartilage volume (day 14), callus volume (day 42) and mineralized bone volume (day 42) and reduced expression of genes associated with endochondral ossification including collagen Type 1 alpha 1, collagen Type 2 alpha 1, vascular endothelial growth factor, Annexin A5, nitric oxide synthase 2, and mechanistic target of rapamycin. Our data suggest that the SDF-1/CXCR4 signaling plays a central role in bone healing possibly by regulating the recruitment and/or differentiation of stem and progenitor cells. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1853-1859, 2012 [ABSTRACT FROM AUTHOR]

R2490 --> Osteoarthritis (OA) is a degenerative joint disease that affects millions of people worldwide. In the United States alone OA affects more than 30 million adults. Several risk factors for OA are well studied, still, there are no therapies to prevent OA. Diabetes mellitus has emerged as a possible risk factor for OA. However, the current literature shows inconsistent results and most of these studies do not address the molecular changes associated with this effect. In addition, most of these studies do not account for changes in body mass index, a well‐known risk factor for OA. In the present study, we first aimed to determine if diabetes is indeed a risk factor for OA, independently of body mass index. Next, we examined diabetes‐related molecular changes in the mouse cartilage knee joints that could contribute to OA. We hypothesized that diabetes would promote OA. Sixteen weeks old streptozotocin‐induced diabetic male mice were assessed for OA and molecular changes in the knee cartilage joint. Cartilage degeneration measurements of the knee joint show a mild OA phenotype in the diabetic group, characterized by proteoglycan loss, when compared to the control group, suggesting that diabetes can moderately promote OA. However, diabetes does not intensify post‐traumatic osteoarthritis induced by a non‐invasive tibial compression injury model. Changes in cartilage knee joint gene expression by RNA sequencing (RNAseq) identified 519 up regulated genes and 645 down regulated genes differentially regulated between diabetic and non‐diabetic animals. This includes known regulators of cartilage and bone remodeling genes such as Col11a2, Col27a1, Mmp28, Adam33, Bglap, Ctsk and Acp5. Our findings suggest that diabetes can be a risk factor for OA, and we identified differential expression of genes that might contribute to the enhanced OA phenotype observed in the diabetic group. This study provides the first account of cartilage knee joint gene expression changes related to diabetes and the risk of OA. Understanding the relationship between diabetes and OA and the molecular changes associated with this can lead to the development of new therapeutic strategies. [ABSTRACT FROM AUTHOR]