HDACi vorinostat protects muscle from degeneration after acute rotator cuff injury in mice.

Aims: Rotator cuff (RC) injuries are characterized by tendon rupture, muscle atrophy, retraction, and fatty infiltration, which increase injury severity and jeopardize adequate tendon repair. Epigenetic drugs, such as histone deacetylase inhibitors (HDACis), possess the capacity to redefine the molecular signature of cells, and they may have the potential to inhibit the transformation of the fibro-adipogenic progenitors (FAPs) within the skeletal muscle into adipocyte-like cells, concurrently enhancing the myogenic potential of the satellite cells. Methods: HDACis were added to FAPs and satellite cell cultures isolated from mice. The HDACi vorinostat was additionally administered into a RC injury animal model. Histological analysis was carried out on the isolated supra- and infraspinatus muscles to assess vorinostat anti-muscle degeneration potential. Results: Vorinostat, a HDACi compound, blocked the adipogenic transformation of muscle-associated FAPs in culture, promoting myogenic progression of the satellite cells. Furthermore, it protected muscle from degeneration after acute RC in mice in the earlier muscle degenerative stage after tenotomy. Conclusion: The HDACi vorinostat may be a candidate to prevent early muscular degeneration after RC injury.

Muscular and Tendon Degeneration after Achilles Rupture: New Insights into Future Repair Strategies.

Achilles tendon rupture is a frequent injury with an increasing incidence. After clinical surgical repair, aimed at suturing the tendon stumps back into their original position, the repaired Achilles tendon is often plastically deformed and mechanically less strong than the pre-injured tissue, with muscle fatty degeneration contributing to function loss. Despite clinical outcomes, pre-clinical research has mainly focused on tendon structural repair, with a lack of knowledge regarding injury progression from tendon to muscle and its consequences on muscle degenerative/regenerative processes and function. Here, we characterize the morphological changes in the tendon, the myotendinous junction and muscle belly in a mouse model of Achilles tendon complete rupture, finding cellular and fatty infiltration, fibrotic tissue accumulation, muscle stem cell decline and collagen fiber disorganization. We use novel imaging technologies to accurately relate structural alterations in tendon fibers to pathological changes, which further explain the loss of muscle mechanical function after tendon rupture. The treatment of tendon injuries remains a challenge for orthopedics. Thus, the main goal of this study is to bridge the gap between clinicians' knowledge and research to address the underlying pathophysiology of ruptured Achilles tendon and its consequences in the gastrocnemius. Such studies are necessary if current practices in regenerative medicine for Achilles tendon ruptures are to be improved.

Proximal tibiofibular joint changes after closed-wedge high tibial osteotomy. Are they relevant?

BACKGROUND: There is some controversy about how the proximal tibiofibular joint (PTFJ) capsulotomy changes PTFJ anatomy in closed-wedge high tibial osteotomy (CW-HTO) and about how this affects ankle and knee mobility and the onset of lateral knee pain. The aim of this study is to evaluate changes in PTFJ after CW-HTO, and its possible clinical significance. METHODS: This study includes 50 patients who underwent CW-HTO with tibiofibular capsulotomy from 2000 to 2018 in our hospital. A clinical evaluation was conducted to evaluate pain location. The degrees of osteoarthritis and the proximal fibular subluxation were evaluated on radiographs. A dynamic analysis of the PTFJ was also performed comparing proximal fibular head subluxation on anteroposterior knee radiographs with the ankle placed in neutral position and dorsiflexed. RESULTS: The clinical evaluation revealed that two patients had a sore scar, five had pain on the PTFJ with manual compression, and none referred lateral compartment pain. The radiological analysis revealed an average proximal subluxation of the fibular head after the osteotomy of 9.64 (range: 0-29) mm, which was greater in oblique PTFJ (p < 0.05). After the surgery, all the patients developed some degree of PTFJ arthritis. There was no correlation between lateral pain and proximal fibular subluxation, tibiofibular arthritis, or lateral compartment arthritis. The dynamic analysis revealed no significant changes. CONCLUSIONS: After CW-HTO all the patients developed proximal subluxation of the fibular head and a variable degree of PTFJ osteoarthritis, but these changes seem to be unrelated with lateral knee pain.