BackgroundAlarmins, endogenous molecules released on tissue damage have been shown to play an important role in inflammatory musculoskeletal conditions including fracture repair andrheumatoid arthritis. However, the contribution of alarmins to the pathogenesis of tendon disease is not fully understood.MethodsWe investigated expression of alarmin proteins (S100A9, high-mobility group box 1 (HMGB1) and interleukin-33 (IL-33) and hypoxia-inducible factor 1α (HIF-1α), a subunit of an oxygen sensitive transcription factor, in three cohorts of human supraspinatus tissues: healthy (n=6), painful diseased (n=13) and post-treatment pain-free tendon samples (n=5). Tissue samples were collected during shoulder stabilisation surgery (healthy) or by biopsy needle (diseased/treated). Immunohistochemistry was used to investigate the protein expression of these factors in these healthy, diseased and treated tendons. Kruskal-Wallis with pairwise post hoc Mann-Whitney U tests were used to test for differences in immunopositive staining between these tissue cohorts. Additionally, costaining was performed to identify the cell types expressing HIF-1α, S100A9, IL-33 and HMGB1 in diseased tendons.ResultsImmunostaining showed HIF-1α and S100A9 were increased in diseased compared with healthy and post-treatment pain-free tendons (p<0.05). IL-33 was reduced in diseased compared with healthy tendons (p=0.0006). HMGB1 was increased in post-treatment pain-free compared with healthy and diseased tendons (p<0.01). Costaining of diseased tendon samples revealed that HIF-1α, S100A9 and IL-33 were expressed by CD68+ and CD68− cells, whereas HMGB1 was predominantly expressed by CD68− cells.ConclusionsThis study provides insight into the pathways contributing to the progressionand resolution of tendon disease. We found potential pro-inflammatory and pathogenic roles for HIF-1α and S100A9, a protective role fornuclear IL-33 and a potentially reparative function for HMGB1 in diseased supraspinatus tendons.

Muscle injuries are common and may be associated with impaired functional capacity, especially among athletes. The results of healing with conventional therapy including rest, ice, compression, and elevation (RICE) are often inadequate, generating substantial interest in the potential for emerging technologies such as platelet-rich plasma (PRP) to enhance the process of soft-tissue healing and to decrease time to recovery. In vitro studies and animal research have suggested that PRP may have benefits associated with the increased release of cytokines and growth factors resulting from supraphysiological concentrations of platelets that facilitate muscle repair, regeneration, and remodeling. Despite the promise of basic science, there is a paucity of clinical data to support the theoretical benefits of PRP. The only double-blind controlled clinical trial was recently reported and showed no benefit of PRP in the time to resume sports activity among athletes with hamstring muscle injury. This review examines the current evidence and the theoretical framework for PRP and muscle healing. Scientific gaps and technological barriers are discussed that must be addressed if the potential promise of PRP as a therapeutic modality for muscle injury is to be realized.

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Background/aimsThe contribution of inflammation to tendinopathy has been debated in the scientific literature. Several factors may contribute to this lack of clarity, including inconsistent definitions of inflammation. We hypothesised that the adoption and/or rejection of a causal link between inflammation and tendinopathy varied as a function of the ‘inflammatory component’ (eg, immune cell and molecular mediators included in published reviews).MethodsTwenty data items were collected from each review to determine conclusions about the role of inflammation in tendinopathy, specific definitions of the ‘inflammatory component,’ quality of the review and other potential correlates. Associations between correlates and a review’s conclusion about the role of inflammation in tendinopathy were tested using binomial logistic regression. The database searches retrieved 2261 unique publications: 137 fulfilled inclusion criteria after full text screenings.ResultsThere has been little support for an inflammatory component to tendinopathy until recently (2012–2015). Prior to 2012, the majority of published reviews did not discuss monocytes, macrophages or lymphocytes in tendinopathy; rather they focused on the lack of neutrophils, often referred to as ‘the inflammatory infiltrate’, or immune cells were not discussed. Reviews including monocytes and lymphocytes in their discussions were 5.23 times more likely to conclude inflammation was important than reviews that did not, p<0.001.ConclusionsData collected show growing support for an inflammatory component to tendinopathy, particularly among high-quality reviews and those that used more robust definitions of inflammation. This finding may have implications for explaining dissonance in the literature regarding a causal role for inflammation in the pathogenesis of tendinopathy.

The purpose of this study is to determine the feasibility of using murine models for translational study of knee ligament injury, repair, and reconstruction. To achieve this aim, we provide objective, quantitative data detailing the gross anatomy, biomechanical characteristics, and microscopic structure of knee ligaments of 44 male mice (C57BL6, 12 weeks of age). Biomechanical testing determined the load-to-failure force, stiffness, and the site of ligament failure for the anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), and the medial and lateral collateral ligaments (MCL and LCL). These data are complemented by histological characterization of each of the knee ligaments. In addition, the osseous morphology of the mouse knee was examined using high-resolution nanofocus computed tomography (CT), while standard micro-CT was employed to measure bone morphometrics of the distal femur and proximal tibia. Collectively, our findings suggest that the gross anatomy of the mouse knee is similar to the human knee despite some minor differences and features unique to the murine knee. The ACL had the highest load to failure (5.60 ± 0.75 N), the MCL (3.33 ± 1.45 N), and the PCL (3.45 ± 0.84 N) were similar, and the LCL (1.44 ± 0.37 N) had the lowest load to failure and stiffness. Murine models provide a unique opportunity to focus on biological processes that impact ligament pathology and healing due to the availability of transgenic strains. Our data support their use as a translational platform for the in vivo study of ligament injury, repair, and reconstruction.