Scar tissue formation secondary to acute muscle injury, surgical wounding and compartment syndrome can result in significant functional impairment and predispose to further injury. The source of fibroblasts, and the molecular mechanisms driving their activation and persistence in skeletal muscle fibrosis are not known. We hypothesized that cells expressing PDGFRβ become fibroblasts in response to injury and that targeting αv integrins in these cells reduces skeletal muscle fibrosis. We used double-fluorescent reporter mice to demonstrate that cells expressing PDGFRβ become activated myofibroblasts in response to cardiotoxin (CTX) induced skeletal muscle injury. Following injury, PDGFRβ+ cells moved from perivascular locations into the interstitium in a distribution characteristic of fibroblasts, and showed marked induction of fibroblastic genes including αSMA and collagen1 (all p<0.0001). To confirm that αv integrins present on PDGFRβ cells critically regulate skeletal muscle fibrosis we used Itgavflox/flox;PDGFRβ-Cre mice (transgenic mice in which αv integrins are ‘knocked-down’ in PDGFRβ+ cells). These mice were significantly protected from CTX induced fibrosis (p<0.01). To demonstrate potential clinical utility of targeting αv integrins, we used a small molecule inhibitor of αv integrins (CWHM12). Treatment with CWHM12 significantly reduced fibrosis when delivered from the time of injury (p<0.01) and when delivered after the fibrotic response had become established (p<0.01). We have identified a core pathway regulating fibrosis in skeletal muscle. Pharmacologic inhibition of αv integrins has potential clinical utility in the treatment and prevention of skeletal muscle fibrosis

Introduction. Many literatures regarding more specific tests to diagnose the supraspinatus tendon injuries and the best rehabilitation methods to strengthen the supraspinatus have been published. However, conflicting results have been reported. 2-deoxy-2-[18F] fluoro-D-glucose (FDG) positron emission tomography (PET) has been recently used to assess skeletal muscle activities in various fields. Purpose. To evaluate & compare the metabolic activities of deltoid & rotator cuff muscles after the full-can & empty-can exercises using PET-CT. Materials and Methods. Ten healthy volunteers (age 27–34/mean 29.8 ± 2.7) with no history of shoulder pain and diabetes mellitus participated in this study. After FDG injection, both arms were maintained in the position of empty can and full can for ten minutes respectively. PET-CT was performed at forty minutes after the injection. The maximum standardized uptake value (SUV) was measured in the anterior, middle and posterior deltoid, supraspinatus, subacapularis and infraspinauts on the entire axial images. Results. The middle deltoid and subscapularis showed significantly greater activity during the empty-can exercise than during the full-can exercise (P=.006 and P=.003 respectively). The muscular activity of the supraspinatus also increased during the empty-can exercise than during the full-can exercise, although no statistical difference existed between two exercises. Six cases of eight cases who had increased activity of the subscapularis had increased activity in superior one half of the subscapularis than in lower one half of it, although there is no significant difference between two portions. Conclusion. The Empty-can exercise requires more strength of the middle deltoid, subscapularis and supraspinatus to keep the arm in internal rotation. The increased activity of the middle deltoid and subscapularis muscles after the empty-can exercise can make the empty-can test less specific to the supraspinatus muscle. The empty-can test can induce pain and weakness due to the subscapularis pathology. The full-can test can be used to test the function of the supraspinatus with the least amount of surrounding middle deltoid and subacapularis muslce activity

Compartment syndrome, a devastating consequence of limb trauma, is characterised by severe tissue injury and microvascular perfusion deficits. We hypothesised that leucopenia might provide significant protection against microvascular dysfunction and preserve tissue viability. Using our clinically relevant rat model of compartment syndrome, microvascular perfusion and tissue injury were directly visualised by intravital video microscopy in leucopenic animals. We found that while the tissue perfusion was similar in both groups (38.8% (standard error of the mean (sem) 7.1), 36.4% (sem 5.7), 32.0% (sem 1.7), and 30.5% (sem 5.35) continuously-perfused capillaries at 45, 90, 120 and 180 minutes compartment syndrome, respectively versus 39.2% (sem 8.6), 43.5% (sem 8.5), 36.6% (sem 1.4) and 50.8% (sem 4.8) at 45, 90, 120 and 180 minutes compartment syndrome, respectively in leucopenia), compartment syndrome-associated muscle injury was significantly decreased in leucopenic animals (7.0% (sem 2.0), 7.0%, (sem 1.0), 9.0% (sem 1.0) and 5.0% (sem 2.0) at 45, 90, 120 and 180 minutes of compartment syndrome, respectively in leucopenia group versus 18.0% (sem 4.0), 23.0% (sem 4.0), 32.0% (sem 7.0), and 20.0% (sem 5.0) at 45, 90, 120 and 180 minutes of compartment syndrome in control, p = 0.0005). This study demonstrates that the inflammatory process should be considered central to the understanding of the pathogenesis of cellular injury in compartment syndrome.

Cite this article: Bone Joint J 2015;97-B:539–43

Heterotopic ossification occurring after the use of commercially available bone morphogenetic proteins has not been widely reported. We describe four cases of heterotopic ossification in patients treated with either recombinant bone morphogenetic protein 2 or recombinant bone morphogenetic protein 7. We found that while some patients were asymptomatic, heterotopic ossification which had occurred around a joint often required operative excision with good results.