Animal models of tendon calcification: Past, present, and future.

Tendon calcification is a common clinical condition that frequently occurs as a complication after tendon injury and surgery, or as an expression of fibrodysplasia ossificans progressiva. This condition can be referred to by various names in clinical practice and literature, including tendon ossification, tendon mineralization, heterotopic ossification, and calcific tendonitis. The exact pathogenesis of tendon calcification remains uncertain, but current mainstream research suggests that calcification is mostly cell mediated. To further elucidate the pathogenesis of tendon calcification and to better simulate the overall process, selecting appropriate experimental animal models is important. Numerous animal models have been utilized in various clinical studies, each with its own set of advantages and limitations. In this review, we have discussed the advancements made in research on animal models of tendon calcification, with a focus on the selection of experimental animals, the sites of injury in these models, and the methods employed for modeling.

Clinical and ultrasonographic evaluation of uninjured dominant shoulder in amateur rugby players vs a control group: a pilot study.

BACKGROUND: Rugby is a sport involving a great number of shoulder collisions. Traumatic stress of the shoulder can weaken the static stabilizers and promote major injuries as dislocation or full-thickness tears of the rotator cuff. The goal of this study is to evaluate the clinical and ultrasonographic dominant shoulder factures in a group of amateur rugby players, with no history of shoulder injuries, and to compare them with those of a control group. METHODS: 52 male subjects join in the study: 26 amateur rugby players and 26 subjects, which did not practice rugby or competitive sport. Clinical history was obtained from all subjects, followed by dominant shoulder physical and ultrasonographic exams. RESULTS: Rugby players showed a higher prevalence of positive clinical test, suggesting subacromial impingement than control group (p = 0.01). Among rugby group, five players (19,2%) showed positive test for radiculopathy (p = 0,02), and ten players (73,1%) reported shoulder pain needing pain-reliever drugs at list one time in the last six months (p = 0.001). In rugby group, ultrasound exams showed 23,1% degenerative changes and 30,8% tendon calcifications in supraspinatus tendons (p < 0.05). CONCLUSIONS: Uninjured dominant shoulder of rugby players shows higher prevalence of clinical and ultrasound changes compare to control. Some rugby players without history of cervical symptoms show positive clinical test of cervical radiculopathy. Clinical and ultrasonographic monitoring of the shoulder can play a role in prevention and knowledge of silent shoulder damage in these athletes.

Controlled-release curcumin attenuates progression of tendon ectopic calcification by regulating the differentiation of tendon stem/progenitor cells.

Tendon calcification is a common but intractable problem leading to pain and activity limitation when injury or tendinopathy progresses into the late stage. This is because tendon stem/progenitor cells (TSPCs) can undergo aberrant osteogenic differentiation under inflammatory conditions. This study aims to investigate the effect of curcumin, a natural anti-inflammatory agent, on regulating the differentiation of TSPCs in tendon calcification. With inflammatory stimulation, TSPCs showed higher alkaline phosphatase activity and more frequent formation of mineralized nodules which were verified in the culture system; however, curcumin significantly alleviated these pathological changes. In in vivo function analysis, chitosan microsphere-encapsulated curcumin was delivered to injured sites of rat tendon ectopic calcification model. The inflammation in the tendon tissues of the curcumin group was significantly relieved. Controlled-release curcumin partially rescued tendon calcification and enhanced tendon regeneration in animal model. This study demonstrates that controlled-release curcumin can manipulate the fate decision of TSPCs, and that it promotes the tenogenesis and inhibits the osteogenesis of TSPCs in a pathological microenvironment, which provides a possible new therapeutic strategy for tendon disease.

Pharmacological Inhibition of Rac1 Activity Prevents Pathological Calcification and Enhances Tendon Regeneration.

Tendinopathy is a common disease, which is characterized by pain, swelling, and dysfunction. At the late stage of tendinopathy, pathological changes may occur, such as tendon calcification. Previously, we have shown that in situ tendon stem/progenitor cells (TSPCs) underwent osteogenesis in the inflammatory niche in diseased tendons. In this study, we demonstrate that this process is accompanied by the activation of Ras-related C3 botulinum toxin substrate 1 (Rac1) signaling. A specific inhibitor NSC23766 significantly downregulated catabolic factors and calcification-related genes and rescued the tenogenesis gene expression of TSPCs under the influence of Interleukin (IL)-1ß in vitro. For in vivo evaluation, we further developed a drug delivery system to encapsulate Rac1 inhibitor NSC23766. Chitosan/ß-glycerophosphate hydrogel encapsulated NSC23766 effectively impeded tendon calcification and enhanced tendon regeneration in rat Achilles tendinosis. Our findings indicated that inhibiting Rac1 signaling could act as an effective intervention for tendon pathological calcification and promote tendon regeneration, thus providing a new therapeutic strategy.

Magnesium inhibits the calcification of the extracellular matrix in tendon-derived stem cells via the ATP-P2R and mitochondrial pathways.

Tendon calcification has been widely regarded by researchers to result from the osteogenic differentiation of Tendon-Derived Stem Cells (TDSCs) and ectopic mineralization caused by the calcification of cellular matrix. Recent studies have revealed a correlation between the Mg(2+)/Ca(2+) balance and the degeneration or calcification of tendon tissues. Furthermore, the ATP-P2X/P2Y receptor pathway has been shown to play a decisive role in the process of calcification, with calcium exportation from mitochondria and calcium oscillations potentially representing the cohesive signal produced by this pathway. Our previous study demonstrated that matrix calcification is inhibited by magnesium. In this study, we examined the effects of extracellular Mg(2+) on the deposition of calcium phosphate matrix and cellular pathways in TDSCs. The suppression of the export of calcium from mitochondria has also been detected. We found that a high concentration of extracellular Mg(2+) ([Mg(2+)]e) inhibited the mineralization of the extracellular matrix in TDSCs and that 100 µM ATP reversed this inhibitory effect in vitro. In addition, the spontaneous release of ATP was inhibited by high [Mg(2+)]e levels. A high [Mg(2+)]e suppressed the expression of P2X4, P2X5 and P2X7 and activated the expression of P2Y1, P2Y2, P2Y4 and P2Y14. The interaction between Mg(2+) and Ca(2+) is therefore contradictory, Mg(2+) inhibits mitochondrial calcium concentrations, meanwhile it reverses the opening of mPTP that is induced by Ca(2+). JC-1 staining verified the protective effect of Mg(2+) on mitochondrial membrane potential and the decrease induced by Ca(2+). Taken together, these results indicate that high [Mg(2+)]e interferes with the expression of P2 receptors, resulting in decreased extracellular mineralization. The balance between Mg(2+) and Ca(2+) influences mitochondrial calcium exportation and provides another explanation for the mechanism underlying matrix calcification in TDSCs.

Current research on tendon calcification / 中华创伤骨科杂志

Tendon calcification,a common clinical disease,is often complicated after tendon injury or surgery,or as a special manifestation of tendinopathy.It is also one manifestation of acquired heterotopic ossification.However,there are no preventive measures for tendon calcification in clinical treatment as its pathogenesis is still unclear.In addition,the domestic orthopedic surgeons have paid little attention to this issue yet.To enhance understanding of tendon calcification,we have summarized the relevant literature published in recent years.

Rectus Femoris Tendon Calcification: Arthroscopic Excision in 6 Top Amateur Athletes.

BACKGROUND: Since it was developed, hip arthroscopy has become the favored treatment for femoroacetabular impingement. Due to recent considerable improvements, the indications for this technique have been widely extended. Injuries of the rectus femoris tendon origin, after an acute phase, could result in a chronic tendinopathy with calcium hydroxyapatite crystal deposition, leading to pain and loss of function. Traditionally, this condition is addressed by local injection of anesthetic and corticosteroids or, when conservative measures fail, by open excision of the calcific lesion by an anterior approach. PURPOSE: To assess whether arthroscopic excision of calcification of the proximal rectus is a safe and effective treatment. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Outcomes were studied from 6 top amateur athletes (age range, 30-43 years; mean, 32.6 years) affected by calcification of the proximal rectus who underwent arthroscopic excision of the calcification. Patients were preoperatively assessed radiographically, and diagnosis was confirmed by a 3-dimensional computed tomography scan. To evaluate the outcome, standardized hip rating scores were used pre- and postoperatively (at 6 and 12 months): the Hip disability and Osteoarthritis Outcome Score, Oxford Hip Score, and Modified Harris Hip Score. Moreover, visual analog scales (VAS) for pain, sport activity level (SAL), and activities of daily living (ADL) were also used. RESULTS: One year after surgery, all patients reported satisfactory outcomes, with 3 of 6 rating their return-to-sport level as high as preinjury level, and the remaining 3 with a percentage higher than 80%. Five patients ranked their ability to carry on daily activities at 100%. Statistical analysis showed significant improvement of the Oxford Hip Score, the Modified Harris Hip Score, and all 3 VAS subscales (pain, SAL, and ADL) from pre- to latest postoperative assessment (P < .05). CONCLUSION: Arthroscopic excision of rectus femoris tendon calcification yields satisfying results with few risks to the patient as well as rapid recovery. CLINICAL RELEVANCE: The recent improvements in hip arthroscopy give the opportunity to address an increasing number of hip conditions effectively and safely, with rapid recovery for the patient. Arthroscopic excision of rectus femoris tendon calcification can be considered a feasible option, with few risks to the patient, rapid recovery, and satisfying outcomes.