Role of the P2X7 Receptor in the Osteogenesis of Heterotopic Ossification of the Achilles Tendon

Background Heterotopic ossification (HO) refers to a painful and complex disease. HO occurs in the setting of persistent systemic inflammation and appears in flare-ups during inflammation, following injury. In the recent research, the P2X7 receptor (P2X7R) is tightly involved in the osteogenesis of periodontal ligament stem cells under the inflammatory conditions. The ionotropic P2X7 receptor (P2X7R) is an ATP-gated ion channel expressed in the majority of stem cells. However, the function of P2X7R in the pathological formation of HO is unclear. Here, this paper hypothesizes that in the model of Achilles tendon ectopic ossification, P2X7R is overexpressed in tendon-derived stem cells and promote osteogenesis of tendon-derived stem cells under inflammatory conditions. Methods The tenotomy puncture and burn injury-induced HO model was constructed. The qPCR and immunofluorescence were used to detect the expression of P2X7R at the site of injured Achilles tendon where HO occurs. Achilles tendon stem cells (SCs) from control group and experimental group sources were cultivated separately under inflammatory conditions. The cells from the two groups were cultured for osteogenic analysis. In addition, a specific antagonist of P2X7R, BBG was used to detect whether reversed the above process. At last, BBG was used to intervene in animal models of heterotopic ossification. Results Under inflammatory conditions, P2X7R expression of the Achilles tendon and osteogenic capability of SCs is higher in heterotopic ossification group (HOG) than in other two groups. The P2X7R expression was positive correlated with the capacity of osteogenesis of SCs. BBG can inhibit osteogenic differentiation and subsequent bone formation in the P2X7R overexpress of SCs. BBG impeded the heterotopic bone formation in animal model. Conclusions P2X7R is one of the crucial mediators in the formation of the HO, blocking which may represent a potential therapeutic target for HO.

An Identical Twin Study on Human Achilles Tendon Adaptation: Regular Recreational Exercise at Comparatively Low Intensities Can Increase Tendon Stiffness

Achilles tendon adaptation is a key aspect of exercise performance and injury risk prevention. However, much debate exists about the adaptation of the Achilles tendon in response to exercise activities. Most published research is currently limited to elite athletes and selected exercise activities. Also, existing studies on tendon adaptation do not control for genetic variation. Our explorative cross-sectional study investigated the effects of regular recreational exercise activities on Achilles tendon mechanical properties in 40 identical twin pairs. Using a handheld oscillation device to determine Achilles tendon mechanical properties, we found that the Achilles tendon appears to adapt to regular recreational exercise at comparatively low intensities by increasing its stiffness. Active twins showed a 28% greater Achilles tendon stiffness than their inactive twin (p < 0.05). Further, our research extends existing ideas on sport-specific adaptation by showing that tendon stiffness seemed to respond more to exercise activities that included an aerial phase such as running and jumping. Interestingly, the comparison of twin pairs revealed a high variation of Achilles tendon stiffness (305.4–889.8 N/m), and tendon adaptation was only revealed when we controlled for genetic variance. Those results offer new insights into the impact of genetic variation on individual Achilles tendon stiffness, which should be addressed more closely in future studies.

Triceps Surae Muscle-Tendon Properties as Determinants of the Metabolic Cost in Trained Long-Distance Runners

Purpose: This study aimed to determine whether triceps surae’s muscle architecture and Achilles tendon parameters are related to running metabolic cost (C) in trained long-distance runners.Methods: Seventeen trained male recreational long-distance runners (mean age = 34 years) participated in this study. C was measured during submaximal steady-state running (5 min) at 12 and 16 km h–1 on a treadmill. Ultrasound was used to determine the gastrocnemius medialis (GM), gastrocnemius lateralis (GL), and soleus (SO) muscle architecture, including fascicle length (FL) and pennation angle (PA), and the Achilles tendon cross-sectional area (CSA), resting length and elongation as a function of plantar flexion torque during maximal voluntary plantar flexion. Achilles tendon mechanical (force, elongation, and stiffness) and material (stress, strain, and Young’s modulus) properties were determined. Stepwise multiple linear regressions were used to determine the relationship between independent variables (tendon resting length, CSA, force, elongation, stiffness, stress, strain, Young’s modulus, and FL and PA of triceps surae muscles) and C (J kg–1m–1) at 12 and 16 km h–1.Results: SO PA and Achilles tendon CSA were negatively associated with C (r2 = 0.69; p < 0.001) at 12 km h–1, whereas SO PA was negatively and Achilles tendon stress was positively associated with C (r2 = 0.63; p = 0.001) at 16 km h–1, respectively. Our results presented a small power, and the multiple linear regression’s cause-effect relation was limited due to the low sample size.Conclusion: For a given muscle length, greater SO PA, probably related to short muscle fibers and to a large physiological cross-sectional area, may be beneficial to C. Larger Achilles tendon CSA may determine a better force distribution per tendon area, thereby reducing tendon stress and C at submaximal speeds (12 and 16 km h–1). Furthermore, Achilles tendon morphological and mechanical properties (CSA, stress, and Young’s modulus) and triceps surae muscle architecture (GM PA, GM FL, SO PA, and SO FL) presented large correlations with C.