Pre-operative gluteus medius tendon degeneration and its impact on strength and functional ability one year after total hip replacement.

OBJECTIVE: Hip osteoarthritis is a common cause of disability and surgery is often unavoidable. Patient satisfaction is high and functional ability improves after surgery. However, residual impairment and pain are common. Degenerative changes in tendons and muscles are probable causes. The aim of this study is to investigate gluteus medius (GMED) tendon degeneration in relation to muscle strength, physical function and walking distance before and one year after total hip replacement. MATERIAL AND METHODS: In total, 18 patients were examined pre- and post-operatively, of whom 15 were available in the final analysis. Muscle strength, physical function and walking distance were assessed. Tendon biopsies were assessed microscopically, and the total degeneration score (TDS) was calculated. RESULTS: A correlation between the TDS and muscle strength was found for the hamstrings, GMED and quadriceps pre- or post-operatively. No correlations were found between the TDS and functional ability. Functional ability and muscle strength improved significantly after surgery. CONCLUSION: Our results indicate a correlation between tendon degeneration and the muscle strength of the hip and knee in patients with hip OA and one year after THR. To minimise post-operative residual discomfort, rehabilitation programs should probably be modified over time to match the pre- and post-operative needs. Further studies are needed.This study was registered at https://www.researchweb.org/is/vgr/project/279039 (in Swedish).

There are negative correlations, which suggest patterns between degeneration in the GMED tendon and muscle strength in the muscles acting around the hip in patients with hip OA, before and after THR.The strength training of muscles acting around the hip joint may need to be adjusted before and after THR.

Enthesopathies - Mechanical, inflammatory or both?

Entheses have the challenging task of transferring biomechanical forces between tendon and bone, two tissues that differ greatly in composition and mechanical properties. Consequently, entheses are adapted to withstand these forces through continuous repair mechanisms. Locally specialized cells (mechanosensitive tenocytes) are crucial in the repair, physiologically triggering biochemical processes to maintain hemostasis. When repetitive forces cause "material fatigue," or trauma exceeds the entheses' repair capacity, structural changes occur, and patients become symptomatic. Clinical assessment of enthesopathies mainly depends on subjective reports by the patient and lacks specificity, especially in patients with central sensitization syndromes. Ultrasonography has been increasingly used to improve the diagnosis of enthesopathies. In this article, the literature on how biomechanical forces lead to entheseal inflammation, including factors contributing to differentiation into a "clinical enthesitis" state and the value of ultrasound to diagnose enthesopathies will be reviewed, as well as providing clues to overcome the pitfalls of imaging.

Challenges and opportunities in testing sensorimotor processing with tendon vibration and transcranial magnetic stimulation in subacromial impingement syndrome: A case series.

BACKGROUND: Non-invasive neurostimulation like muscle tendon vibration (VIB) and transcranial magnetic stimulation (TMS) can provide valuable insights on mechanisms underlying sensorimotor dysfunctions. However, their feasibility in the context of painful musculoskeletal disorders like shoulder impingement syndrome (SIS) remain uncertain. METHODS: The present work used a case series design including 15 participants with SIS, as well as a secondary group-based analysis comparing participants with SIS to 15 healthy counterparts. Proprioceptive processing was tested by VIB-induced kinesthetic illusions of shoulder abduction, and TMS tested corticospinal excitability of the upper trapezius. Detailed individual data were collected, including any technical challenges and feasibility issues encountered. RESULTS: VIB was in general well-tolerated and elicited a perceptible kinesthetic illusion in 13 participants with SIS and 14 controls. TMS presented with several challenges related to discomfort, fear-related behaviors, technical problems and high motor thresholds, especially in participants with SIS. It was only possible to collect all TMS measures in 5 participants with SIS (for both the painful and non/less-painful sides), in 7 controls on their dominant side and 10 controls on the non-dominant side. The only significant group-based analysis was a lower illusion speed/amplitude on the painful versus non-painful side in persons with SIS (p = 0.035). CONCLUSION: Our study provides preliminary data on challenges encountered with TMS and VIB of trunk/proximal muscle in persons with SIS and healthy counterparts. It might help future studies to better address those challenges beforehand and improve the overall feasibility and impact of neurostimulation tools in musculoskeletal disorders.

Widespread Pressure Pain Hyperalgesia Is Not Associated With Morphological Changes of the Wrist Extensor Tendon in Unilateral Lateral Epicondylalgia: A Case-Control Study.

OBJECTIVE: The aims of the current study were to investigate the presence of widespread pressure hyperalgesia, the presence of structural changes in the wrist extensor tendon and muscle, and their association in people with lateral epicondylalgia (LE). METHODS: Thirty-seven patients with LE (43% women; mean age = 45.5 [SD = 9.5] years) and 37 controls matched for age and sex and free of pain participated in this study. Pressure pain thresholds (PPTs) were assessed bilaterally over the symptomatic area (elbow), 2 segment-related areas (C5-C6 joint, second intermetacarpal space), and 1 remote area (tibialis anterior) in a blinded design. Ultrasound measurements (eg, cross-sectional area, thickness, and width) of the common wrist extensor tendon and extensor carpi radialis brevis muscle as well as the thickness of the supinator muscle were assessed. RESULTS: Patients with LE exhibited lower PPTs bilaterally at all points and lower PPTs at the lateral epicondyle and second intermetacarpal space on the symptomatic side as compared to the nonsymptomatic side (η2 from 0.123-0.369; large effects). Patients exhibited higher cross-sectional area and width of the common wrist extensor tendon (η2 from 0.268-0.311; large effects) than controls bilaterally, whereas tendon thickness was also higher (η2 = 0.039; small effects) on the painful side than on the nonpainful side. CONCLUSIONS: This study reported bilateral widespread pressure pain hyperalgesia and morphological changes in the tendon, but not the muscle, in LE. Pressure pain sensitivity and morphological changes were not associated in individuals with LE. IMPACT: Management of LE should consider altered nociceptive pain processing and structural tendon changes as 2 different phenomena in patients with LE.

[A quantitative study of mechanics in the treatment of atlantoaxial joint disorder by tendon relaxation manipulation].

OBJECTIVE: To explore dose-effect relationship of biomechanical parameters in treating atlantoaxial joint disorder by slimming manipulation. METHODS: From October 2022 to May 2023, 18 patients with atlantoaxial joint disorders were treated, including 10 males and 8 females;aged from 24 to 27 years old with an average of (25.50±1.10) years old;CT of cervical vertebra showed 16 patients with right side distortion and 2 patients with left side distortion. The mechanical parameters of treatment of atlantoaxial joint disorder by tendon relaxation manipulation were measured by wearing massage manipulation gloves. The magnitude, frequency and mechanical curve of force during tendon relaxation and starting force, pulling force, pulling time and mechanical curve during rehabilitation were quantified, the differences between the affected and contralateral manipulations were compared. RESULTS: The maximum force and frequency of Fengchi(GB20) on the affected side were (19.82±2.02) N and (116.83±14.49) times/min, and opposite side were (13.87±2.19) N and (188.89±16.03) times/min, respectively. There were statistically difference in the maximum force and frequency of both sides (P<0.05). The maximum force and frequency of Quepen (ST12) on the affected side were (14.44±3.27) N and (139.06±28.47) times/min, and those on the opposite side were (9.41±1.38) N and (142.50±28.47) times/min. There was difference in maximum force on both sides (P<0.05). The starting force, turning force and turning time of the affected side were (14.16±5.98) N, (11.56±6.63) N, (0.14±0.03) S, and the contralateral side were (8.94±3.39) N, (8.30±4.64) N, (0.18±0.04) S, respectively. The difference of starting force, turning force and turning time on both sides were statistically significant (P<0.05). CONCLUSION: By applying a light relaxation force on the affected side, the mechanical balance between cervical vertebrae could be restored, and recovery trend of atlantoaxial joint disorder could be strengthened. On this basis, the atlantoaxial odontoid process could be reversed by applying a light rotation force, which reflects the characteristics of high safety of the manipulation.

Pathomechanics of lumbrical and flexor digitorum profundus muscle tears in climbers: A cadaveric model.

Lumbrical muscles originate on the flexor digitorum profundus (FDP) tendons and, during fist making, they move in the same direction when FDP muscle produces maximal proximal tendon gliding. Injuries of the bipennate lumbricals have been described when a shear force acts between the origins on adjacent tendons of the FDP, as they glide in opposite directions in asymmetric hand postures. Other structures of the deep flexors complex can be affected during this injury mechanism, due to the so-called quadriga effect, which can commonly occur during sport climbing practise. Biomechanical studies are needed to better understand the pathomechanism. A cadaveric study was designed to analyse the effects of load during the fourth lumbrical muscle injury mechanism. The amount of FDP tendon gliding and metacarpophalangeal (MCP) joint flexion of the 5th finger were calculated. Ten fresh-frozen cadaveric specimens (ten non-paired forearms and hands) were used. The specimens were placed on a custom-made loading apparatus. The FDP of the 5th finger was loaded, inducing isolated flexion of the 5th finger, until rupture. The rupture occurred in all specimens, under a load of 11 kg (SD 4.94), at 9.23 mm of proximal tendon gliding (SD 3.55) and at 21.4° (SD 28.91) of MCP joint flexion. Lumbrical muscle detachment from the 4th FDP was observed, from distal to proximal, and changes in FDP tendons at the distal forearm level too. The quadriga effect can lead to injury of the bipennate lumbrical muscles and the deep flexors complex in the hand and forearm.

Neuronal regulation of bone and tendon injury repair: a focused review.

Beyond the sensation of pain, peripheral nerves have been shown to play crucial roles in tissue regeneration and repair. As a highly innervated organ, bone can recover from injury without scar formation, making it an interesting model in which to study the role of nerves in tissue regeneration. As a comparison, tendon is a musculoskeletal tissue that is hypo-innervated, with repair often resulting in scar formation. Here, we reviewed the significance of innervation in 3 stages of injury repair (inflammatory, reparative, and remodeling) in 2 commonly injured musculoskeletal tissues: bone and tendon. Based on this focused review, we conclude that peripheral innervation is essential for phases of proper bone and tendon repair, and that nerves may dynamically regulate the repair process through interactions with the injury microenvironment via a variety of neuropeptides or neurotransmitters. A deeper understanding of neuronal regulation of musculoskeletal repair, and the crosstalk between nerves and the musculoskeletal system, will enable the development of future therapies for tissue healing.

Accumulating evidence has shown that, across organs systems, peripheral nerves regulate the process of tissue repair and regeneration. This is particularly relevant in the context of musculoskeletal injuries such as those affecting the bone and tendon. The question then arises: what is the function of peripheral innervation in the repair of bone and tendon injuries? This review offers an in-depth look at the ways in which nerves regulate the healing of bone and tendon injuries at various stages of recovery. A deeper comprehension of the influence of nerves on the repair of these tissues could pave the way for the development of future therapeutic strategies for tissue healing.

Exploring the Link Between Autophagy-Lysosomal Dysfunction and Early Heterotopic Ossification in Tendons.

Heterotopic ossification (HO), the pathological formation of bone within soft tissues such as tendon and muscle, is a notable complication resulting from severe injury. While soft tissue injury is necessary for HO development, the specific molecular pathology responsible for trauma-induced HO remains a mystery. The previous study detected abnormal autophagy function in the early stages of tendon HO. Nevertheless, it remains to be determined whether autophagy governs the process of HO generation. Here, trauma-induced tendon HO model is used to investigate the relationship between autophagy and tendon calcification. In the early stages of tenotomy, it is observed that autophagic flux is significantly impaired and that blocking autophagic flux promoted the development of more rampant calcification. Moreover, Gt(ROSA)26sor transgenic mouse model experiments disclosed lysosomal acid dysfunction as chief reason behind impaired autophagic flux. Stimulating V-ATPase activity reinstated both lysosomal acid functioning and autophagic flux, thereby reversing tendon HO. This present study demonstrates that autophagy-lysosomal dysfunction triggers HO in the stages of tendon injury, with potential therapeutic targeting implications for HO.

Reliability of an intraoral extension for intraoral palpation and assessment of mechanical sensitivity of the temporal tendon.

BACKGROUND: The temporal tendon is a structure often compromised in patients suffering from temporomandibular disorders (TMD), yet its intraoral location makes a standardised assessment difficult. OBJECTIVES: To evaluate the variability and accuracy to target force of a newly designed intraoral extension for a palpometer device (Palpeter, Sunstar Suisse) when compared to manual palpation, in addition to clinically assessing the mechanical sensitivity and referred sensations of the temporal tendon in healthy individuals. METHODS: Experiment 1: 12 individuals were asked to target on a scale 0.5, 1 and 2 kg, for 2 and 5 s by using five different methods (Palpeter, Palpeter with three different extension shapes and manual palpation). Experiment 2: 10 healthy participants were recruited for a randomised double-blinded assessment by applying pressure of 0.5, 1 and 2 kg to the right temporal tendon with the three extensions and manual palpation. Participants rated the intensity of their sensation/pain on a 0-50-100 numeric rating scale (NRS), unpleasantness on a 0-100 NRS, and if present, they rated and drew the location of referred sensations. Repeated measures analysis of variance (ANOVA) was used in both experiments to compare differences between palpation methods. Tukey's HSD tests were used for the post hoc comparisons, and p values below .05 were considered significant. RESULTS: Experiment 1: The extensions showed no significant differences between them regarding reliability and accuracy for all forces and durations (p > .05). The manual method was significantly less reliable and accurate when compared to the other methods (p < .05). Experiment 2: There were no significant differences between the Palpeter extensions regarding pain intensity or unpleasantness NRS scores (p > .05), but all the extensions had significantly increased pain intensity and unpleasantness when compared to manual palpation (p < .05). Similarly, the frequency of referred sensations was similar between extensions but increased when compared to manual palpation. CONCLUSIONS: The new Palpeter extensions proved to be significantly more accurate and have lower test-retest variability than the manual method in a non-clinical setting. Clinically, they showed no significant differences in NRS scores for pain intensity nor unpleasantness, with no major differences in referred sensations, making any of the extensions suitable for clinical testing of the temporal tendon in future studies.

All-suture anchor size and drill angle influence load to failure in a porcine model of subpectoral biceps tenodesis, a biomechanical study.

BACKGROUND: Tenodesis of the long head of the biceps tendon is frequently performed in shoulder surgery, and all-suture anchors have become more popular as fixation methods. However, uncertainty still exists regarding the ultimate load to failure of all-suture anchors and the best insertion angle at a cortical humeral insertion point. PURPOSE: The purpose of this study was to compare the biomechanical characteristics of three types of all-suture anchors frequently used for biceps tenodesis. In addition, the influence of two different insertion angles was observed in a porcine humeri model. METHODS: The ultimate load to failure and failure mode of three types of all-suture anchors (1.6 FiberTak®, 1.9 FiberTak®, 2.6 FiberTak®, Arthrex®) applicable for subpectoral biceps tenodesis were evaluated at 90° and 45° insertion angles in 12 fresh-frozen porcine humeri. The anchors were inserted equally alternated in a randomized manner at three different insertion sites along the bicipital groove, and the suture tapes were knotted around a rod for pullout testing. In total, 36 anchors were evaluated in a universal testing machine (Zwick & Roell). RESULTS: The 2.6 FiberTak® shows higher ultimate loads to failure with a 90° insertion angle (944.0 N ± 169.7 N; 537.0 N ± 308.8 N) compared to the 1.9 FiberTak® (677.8 N ± 57.7 N; 426.3 N ± 167.0 N, p-value: 0.0080) and 1.6 FiberTak® (733.0 N ± 67.6 N; 450.0 N ± 155.8 N, p-value: 0.0018). All anchor types show significantly higher ultimate loads to failure and smaller standard deviations at the 90° insertion angle than at the 45° insertion angle. The major failure mode was anchor pullout. Only the 2.6 FiberTak® anchors showed suture breakage as the major failure mode when placed with a 90° insertion angle. CONCLUSIONS: All three all-suture anchors are suitable fixation methods for subpectoral biceps tenodesis. Regarding our data, we recommend 90° as the optimum insertion angle. CLINICAL RELEVANCE: The influence of anchor size and insertion angle of an all-suture anchor should be known by the surgeon for optimizing ultimate loads to failure and for achieving a secure fixation.

Biomechanics Explains Variability of Response of Small Hypertropia to Graded Vertical Rectus Tenotomy.

PURPOSE: Small angle hypertropia in sagging eye syndrome is conveniently treated by graded vertical rectus tenotomy, yet an adjustable technique under topical anesthesia has been recommended because of variability of effect. We performed graded tenotomy in an experimental model to elucidate the reason for variability of response to this surgical procedure. DESIGN: Experimental study. METHODS: Thirty-two fresh bovine rectus musculotendon specimens were prepared including continuity with insertional sclera, and extending for a total 40 mm length to the proximal muscle bellies, and trimmed to 16 mm width. Specimens were anchored by the clamps at the scleral insertion and muscle belly ends within a physiological chamber. After preconditioning and elongation to 10% strain was imposed by a linear motor, tensile force was allowed to stabilize at a plateau state. Then 25%, 50%, 75%, 90%, and 100% marginal tenotomies were performed progressively as remnant forces were measured. RESULTS: Tendon thickness averaged 0.29 ± 0.05 mm and width 19.71 ± 2.25 mm. On average, remnant force decreased linearly (R2 = 0.985) from 4.23 ± 1.34, 2.76 ± 0.88, 1.70 ± 0.73, 1.01 ± 0.49, 0.39 ± 0.10, and 0 N, at 0%, 25%, 50%, 75%, 90%, and 100% tenotomy. However, there was marked individual variability in effect among specimens, with coefficients of variation of 32%, 32%, 43%, 49%, and 27%, respectively. CONCLUSION: On average, there is a linear relationship between graded rectus tenotomy and percentage force reduction, but the effect among individual tendons is large, paralleling the reported variation in surgical effect. This explains and implies continued advisability of adjustable technique in this procedure.

De Quervain tendinitis after total trapeziometacarpal joint arthroplasty: Biomechanical evaluation of tendon excursion in the first extensor tendon compartment.

De Quervain's tenosynovitis is the most common complication after total trapeziometacarpal joint replacement. Etiology is unclear. Implantation of a ball-in-socket implant changes the biomechanics of the normal trapeziometacarpal saddle joint and increases its range of motion. The present study demonstrates that this procedure also significantly increases excursion of the abductor pollicis longus and extensor pollicis brevis tendons during thumb flexion-extension, and not during thumb abduction-adduction. Increased tendon gliding under the retinaculum of the first extensor tendon compartment could predispose to the development frictional tenosynovitis and play a role in the development of de Quervain's syndrome after total trapeziometacarpal joint replacement. LEVEL OF EVIDENCE: Not applicable (laboratory study).

The Iliopsoas: Anatomy, Clinical Evaluation, and Its Role in Hip Pain in the Athlete: A Scoping Review.

Disability due to iliopsoas (IP) pain and dysfunction is underdiagnosed in the athletic population. The IP unit consists of the psoas major and iliacus muscles converging to form the IP tendon and is responsible primarily for hip flexion strength but has a number of secondary contributions such as femoral movement, trunk rotation, core stabilization, and dynamic anterior stability to the hip joint. As the IP passes in front of the anterior acetabulum and labrum, the diagnosis of IP pain may be confused with labral tearing seen on magnetic resonance imaging. This is in addition to the low sensitivity of magnetic resonance imaging to detect IP tendinitis and bursitis. Resisted seated hip flexion as well as direct palpation of the IP tendon and muscle belly are useful to assess function and help determine whether the IP may be the source of pain, which is common in athletes. Both biomechanical and clinical investigations have demonstrated the role of IP as an anterior hip stabilizer. Patients with signs of hip microinstability, developmental dysplasia of the hip, and increased femoral anteversion are at risk of IP pain and poor outcomes after IP lengthening, highlighting the importance of the IP in providing dynamic anterior hip stability.

Wrist extensor pathomechanics: implications for tendon and nerve transfer.

Central and peripheral nervous system lesions may disrupt the intricate balance of the prime movers of the wrist. In spasticity, hyperactive wrist flexors create a flexion moment and, if untreated, can lead to flexion contractures. In patients with C6 spinal cord injury and tetraplegia, the posterior interosseus nerve is typically affected by a complex pattern of upper and/or lower motoneuron lesions causing radial deviation of the wrist due to loss of ulnar deviation actuators. In this report, we illustrate severe pathomechanics that may occur even with relatively modest changes in wrist balance. These results illustrate how thorough understanding of muscle-tendon-joint interaction aids in designing tendon and nerve reconstructive surgeries to normalize wrist positions and balance in neuromuscular conditions.

EMG-Constrained and Ultrasound-Informed Muscle-Tendon Parameter Estimation in Post-Stroke Hemiparesis.

Secondary morphological and mechanical property changes in the muscle-tendon unit at the ankle joint are often observed in post-stroke individuals. These changes may alter the force generation capacity and affect daily activities such as locomotion. This work aimed to estimate subject-specific muscle-tendon parameters in individuals after stroke by solving the muscle redundancy problem using direct collocation optimal control methods based on experimental electromyography (EMG) signals and measured muscle fiber length. Subject-specific muscle-tendon parameters of the gastrocnemius, soleus, and tibialis anterior were estimated in seven post-stroke individuals and seven healthy controls. We found that the maximum isometric force, tendon stiffness and optimal fiber length in the post-stroke group were considerably lower than in the control group. We also computed the root mean square error between estimated and experimental values of muscle excitation and fiber length. The musculoskeletal model with estimated subject-specific muscle tendon parameters (from the muscle redundancy solver), yielded better muscle excitation and fiber length estimations than did scaled generic parameters. Our findings also showed that the muscle redundancy solver can estimate muscle-tendon parameters that produce force behavior in better accordance with the experimentally-measured value. These muscle-tendon parameters in the post-stroke individuals were physiologically meaningful and may shed light on treatment and/or rehabilitation planning.

Tendones peroneos: una revisión contemporánea / Peroneal tendons. Contemporary update

La patología de peroneos es compleja y frecuentemente subdiagnosticada. El conocimiento detallado de la anatomía, biomecánica y fisiopatología es fundamental para realizar un correcto diagnóstico y tratamiento. El objetivo de este artículo es revisar la información más actualizada sobre la patología de los tendones peroneos (tendinopatía, inestabilidad y rotura).

Pathology of the peroneal tendons is complex and often underdiagnosed. Knowledge of anatomy, biomechanics, and physiopathology is necessary for diagnosing and treating this condition. The objective of this article is to review the most updated information regarding peroneal tendon pathology (tendinopathy, dislocation/subluxation, and tears), which may help managing patients with lateral pain of the foot and ankle.

Tendon Healing in a Mouse Model of Loeys-Dietz Syndrome: Controlled Study Using a Patellar Tendon Transection Model.

BACKGROUND: Loeys-Dietz syndrome (LDS) is a rare autosomal-dominant connective tissue disorder caused by genetic mutations in the transforming growth factor-ß (TGFß) signaling pathway. In addition to vascular malformations, patients with LDS commonly present with bone and tendon abnormalities, including joint laxity. While TGFß signaling dysregulation has been implicated in many of these clinical manifestations, the degree to which it influences the tendinopathy and tendon healing issues in LDS has not been determined. METHODS: Wound healing after patellar tendon transection was compared between wild-type (WT) and Tgfbr2-mutant (LDS) mice (7 mice per group). In all mice, the right patellar tendon was transected at midsubstance, while the left was untouched to serve as a control. Mice were euthanized 6 weeks after surgery. Tendon specimens were harvested for histopathologic grading according to a previously validated scoring metric, and gene expression levels of Mmp2, Tgfb2, and other TGFß-signaling genes were assayed. Between-group comparisons were made using 1-way analysis of variance with post hoc Tukey honestly significant difference testing. RESULTS: Expression levels of assayed genes were similar between LDS and WT tendons at baseline; however, at 6 weeks after patellar tendon transection, LDS tendons showed sustained elevations in Mmp2 and Tgfb2 compared with baseline values; these elevations were not seen in normal tendons undergoing the same treatments. Histologically, untreated LDS tendons had significantly greater cellularity and cell rounding compared with untreated WT tendons, and both WT and LDS tendons had significantly worse histologic scores after surgery. CONCLUSION: We present the first mechanistic insight into the effect of LDS on tendons and tendon healing. The morphologic differences between LDS and WT tendons at baseline may help explain the increased risk of tendon/ligament dysfunction in patients with LDS, and the differential healing response to injury in LDS may account for the delayed healing and weaker repair tissue. LEVEL OF EVIDENCE: Level V.

A Hyperglycemic Microenvironment Inhibits Tendon-to-Bone Healing through the let-7b-5p/CFTR Pathway.

BACKGROUND: Tendon-to-bone healing is a difficult process in treatment of rotator cuff tear (RCT). In addition, diabetes is an important risk factor for poor tendon-to-bone healing. Therefore, we investigated the specific mechanisms through which diabetes affects tendon-to-bone healing by regulating the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). METHODS: Tendon-derived stem cells (TDSCs) were extracted from rats after which their proliferative capacities were evaluated by the MTT assay. The expression levels of CFTR and tendon-related markers were determined by qRT-PCR. Then, bioinformatics analyses and dual luciferase reporter gene assays were used to identify miRNAs with the ability to bind CFTR mRNA. Finally, CFTR was overexpressed in TDSCs to validate the specific mechanisms through which the high glucose microenvironment inhibits tendon-to-bone healing. RESULTS: The high glucose microenvironment downregulated mRNA expression levels of tendon-related markers and CFTR in TDSCs cultured with different glucose concentrations. Additionally, bioinformatics analyses revealed that let-7b-5p may be regulated by the high glucose microenvironment and can regulate CFTR levels. Moreover, a dual luciferase reporter gene assay was used to confirm that let-7b-5p targets and binds CFTR mRNA. Additional experiments also confirmed that overexpressed CFTR effectively reversed the negative effects of the hyperglycaemic microenvironment and upregulation of let-7b-5p on TDSC proliferation and differentiation. These findings imply that the hyperglycemic microenvironment inhibits CFTR transcription and, consequently, proliferation and differentiation of TDSCs in vitro by upregulating let-7b-5p. CONCLUSIONS: A hyperglycemic microenvironment inhibits TDSC proliferation in vitro via the let-7b-5p/CFTR pathway, and this is a potential mechanism in diabetes-induced poor tendon-to-bone healing.

Eugenol-Preconditioned Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Antioxidant Capacity of Tendon Stem Cells In Vitro and In Vivo.

Tendon stem cells (TSCs) are often exposed to oxidative stress at tendon injury sites, which impairs their physiological effect as well as therapeutic application. Recently, extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells (BMSCs) were shown to mediate cell protection and survival under stress conditions. The function of BMSC-EVs may be affected by pretreatment with various factors such as eugenol (EUG)-a powerful antioxidant. In our previous study, we found that H2O2 significantly impaired TSC proliferation and tenogenic differentiation capabilities. Apoptosis and intracellular ROS accumulation in TSCs were induced by H2O2. However, such H2O2-induced damage was prevented by treatment with EUG-BMSC-EVs. Furthermore, EUG-BMSC-EVs activated the Nrf2/HO-1 pathway to counteract H2O2-induced damage in TSCs. In a rat patellar tendon injury model, the ROS level was significantly higher than that in the normal tendon and TSCs not pretreated showed a poor therapeutic effect. However, EUG-BMSC-EV-pretreated TSCs significantly improved tenogenesis and matrix regeneration during tendon healing. Additionally, the EUG-BMSC-EV group had a significantly improved fiber arrangement. Overall, EUG-BMSC-EVs protected TSCs against oxidative stress and enhanced their functions in tendon injury. These findings provide a basis for potential clinical use of EUG-BMSC-EVs as a new therapeutic vehicle to facilitate TSC therapies for tendon regeneration.

Extracorporeal Shockwave Therapy With a Modified Technique on Tendon and Ligament for Knee Osteoarthritis: A Randomized Controlled Trial.

BACKGROUND: There have been no definitive guidelines on the treatment method and specific points in the body. PURPOSE: The aim of the study was to investigate the effects of extracorporeal shockwave therapy on treating the main tendons and ligaments of knee osteoarthritis. METHOD: A total of 36 patients with knee osteoarthritis were enrolled in trial and organized into two groups: 3-wk extracorporeal shockwave therapy for the intervention group and 3-wk sham extracorporeal shockwave therapy for control group. Both groups received the same physical therapies: (1) transcutaneous electrical nerve stimulation, (2) magnetic field treatment, and (3) quadricep muscle strength training. Evaluation was performed before the start of treatment, at third week after the start of treatment, and 1 wk after the end of treatment. The study used randomized controlled trials (level of evidence, 1). RESULT: Eextracorporeal shockwave therapy group had significant improvement in WOMAC pain score, physical function, and total score (mean difference = -2.8, P < 0.001; -5.1, P = 0.02; -8.3, P = 0.004, respectively), Visual Analog Scale score (mean difference = -2.3, P < 0.001), and the distance of 6-min walk test (mean difference = 28.7, P = 0.01) in the 1 wk after the end of treatment. Statistical significance in WOMAC pain, physical function, and total scores (mean difference = -3.0, P = 0.001; -5.6, P = 0.02; -9.3, P = 0.004, respectively) and Visual Analog Scale score (mean difference = -1.2, P = 0.027) was observed between the extracorporeal shockwave therapy group and control group. CONCLUSIONS: Extracorporeal shockwave therapy for the tendons and ligaments has clinical benefits for pain and physical function improvement in knee osteoarthritis. In addition, improvement in physical performance was observed in the short-term follow-up.