Both osteoporosis and tendinopathy are widely prevalent disorders, encountered in diverse medical contexts. Whilst each condition has distinct pathophysiological characteristics, they share several risk factors and underlying causes. Notably, oxidative stress emerges as a crucial intersecting factor, playing a pivotal role in the onset and progression of both diseases. This imbalance arises from a dysregulation in generating and neutralising reactive oxygen species (ROS), leading to an abnormal oxidative environment. Elevated levels of ROS can induce multiple cellular disruptions, such as cytotoxicity, apoptosis activation and reduced cell function, contributing to tissue deterioration and weakening the structural integrity of bones and tendons. Antioxidants are substances that can prevent or slow down the oxidation process, including Vitamin C, melatonin, resveratrol, anthocyanins and so on, demonstrating potential in treating these overlapping disorders. This comprehensive review aims to elucidate the complex role of oxidative stress within the interlinked pathways of these comorbid conditions. By integrating contemporary research and empirical findings, our objective is to outline new conceptual models and innovative treatment strategies for effectively managing these prevalent diseases. This review underscores the importance of further in-depth research to validate the efficacy of antioxidants and traditional Chinese medicine in treatment plans, as well as to explore targeted interventions focused on oxidative stress as promising areas for future medical advancements.

Tendinitis, characterized by the inflammation of tendons, poses significant challenges in both diagnosis and treatment due to its multifaceted etiology and complex pathophysiology. This study aimed to dissect the molecular mechanisms underlying tendinitis, with a particular focus on inflammasome-related genes and their interactions with the immune system. Through comprehensive gene expression analysis and bioinformatics approaches, we identified distinct expression profiles of inflammasome genes, such as NLRP6, NLRP1, and MEFV, which showed significant correlations with immune checkpoint molecules, indicating a pivotal role in the inflammatory cascade of tendinitis. Additionally, MYD88 and CD36 were found to be closely associated with HLA family molecules, underscoring their involvement in immune response modulation. Contrary to expectations, chemokines exhibited minimal correlation with inflammasome genes, suggesting an unconventional inflammatory pathway in tendinitis. Transcription factors like SP110 and CREB5 emerged as key regulators of inflammasome genes, providing insight into the transcriptional control mechanisms in tendinitis. Furthermore, potential therapeutic targets were identified through the DGidb database, highlighting drugs that could modulate the activity of inflammasome genes, offering new avenues for targeted tendinitis therapy. Our findings elucidate the complex molecular landscape of tendinitis, emphasizing the significant role of inflammasomes and immune interactions, and pave the way for the development of novel diagnostic and therapeutic strategies.

UNASSIGNED: The purpose of this study was to determine whether TLR4 knockdown induced by miRNA-140-5p improves tendinopathy in an in vitro experiment.
UNASSIGNED: Extraction of tendon-derived stem cells (TDSCs) from SD rats was performed using TGF-β1 to develop a tendinopathy cell model. In the first step, we knocked down TLR4 by si-TLR4 to investigate TLR4 in tendinopathy development, and the next we used miRNA-140-5p to investigate miRNA-140-5p in tendinopathy development. The inflammatory factors and Hyp concentration were evaluated by ELISA assay; the cell viability was measured by MTT assay; the cell apoptosis was evaluated by TUNEL and/or flow cytometry. The relative mRNA was measured by RT-qPCR assay; the relative proteins expression was evaluated by cellular immunofluorescence and/or WB assay. The correlation between miRNA-140-5p and TLR4 was analyzed by Luciferase reporter assay.
UNASSIGNED: With miRNA-140-5p overexpression or TLR4 knockdown, the cell viability was significantly increased with cell apoptosis depressing compared with the Model group (p < 0.05, respectively). Meanwhile, the inflammatory factors TNF-α, IL-1β and IL-6 and Hyp concentration were significantly improved (p < 0.05, respectively), whereas the TLR4, MyD88 and NF-κB(p65) protein expression levels were significantly depressed with TLR4 knockdown by si-TLR4 or miRNA-140-5p which target TLR4.
UNASSIGNED: The present results showed that TLR4 knockdown induced by miRNA-140-5p or si-TLR4 improved tendinopathy in an in vitro cell experiment.

BACKGROUND: One of the most prevalent illnesses of the shoulder is rotator cuff tendinosis, which is also a major contributor to shoulder discomfort and shoulder joint dysfunction. According to statistics, rotator cuff tendinosis occurs in 0.3-5.5% of cases and affects 0.5-7.4% of people annually. It will be necessary to conduct a meta-analysis to evaluate the efficacy of hypertonic glucose proliferation therapy in the treatment of rotator cuff problems.
METHODS: The databases Cochrane PubMed, Library, Web of Science and EMbase, are retrieved by the computer. Individuals with rotator cuff lesions in the intervention group were treated with hypertonic dextrose proliferation therapy, whereas individuals in the control condition were treated with a placebo. Outcome markers for rotator cuff lesions patients; Pursuant to studies, the visual analogue scale (VAS) score, the shoulder pain & disability index (SPADI), & other metrics are used to evaluate the effects of hypertonic dextrose proliferation treatment on individuals with rotator cuff diseases. After carefully evaluating the calibre of the literature, data analysis was performed utilising the RevMan 5.3 programme.
RESULTS: Meta-analysis finally contained 6 papers. In six investigations, the test & control group\'s VAS scores improved, with the test team\'s score considerably outperforming the control team [standardized mean difference (SMD): 1.10; 95% Cl: 0.37,1.83; P < 0.01], shoulder pain and disability index (SPADI) score (SMD:8.13; 95% Cl: 5.34,10.91; P < 0.01), Flexion (SMD:5.73; 95% Cl: 0.99,10.47; P < 0.05), Abduction (SMD:6.49; 95% Cl: 0.66,12.31; P < 0.05), Internal rotation (SMD:-1.74; 95% Cl: -4.25,0.78; P = 0.176) and External rotation (SMD:2.78; 95% Cl: -0.13,5.69; P = 0.062).
CONCLUSIONS: The findings of this study suggest that individuals with rotator cuff injuries may benefit from hypertonic dextrose proliferation treatment based on the visual analogue scale (VAS) score, the Shoulder Pain and Disability Index (SPADI) score, Flexion, & Abduction. These results must, nevertheless, be supported by high-caliber follow-up research.

OBJECTIVE: There is increasing evidence that type 2 diabetes mellitus (T2DM) is an independent risk factor for the occur of tendinopathy. Therefore, this study is the first to explore the dynamic changes of the \"gene profile\" of supraspinatus tendon in rats at different time points after T2DM induction through transcriptomics, providing potential molecular markers for exploring the pathogenesis of diabetic tendinopathy.
METHODS: A total of 40 Sprague-Dawley rats were randomly divided into normal (NG, n = 10) and T2DM groups (T2DM, n = 30) and subdivided into three groups according to the duration of diabetes: T2DM-4w, T2DM-8w, and T2DM-12w groups; the duration was calculated from the time point of T2DM rat model establishment. The three comparison groups were set up in this study, T2DM-4w group vs. NG, T2DM-8w group vs. NG, and T2DM-12w group vs. NG. Differentially expressed genes (DEGs) in 3 comparison groups were screened. The intersection of the three comparison groups\' DEGs was defined as key genes that changed consistently in the supraspinatus tendon after diabetes induction. Cluster analysis, gene ontology (GO) functional annotation analysis and Kyoto encyclopedia of genes and genomes (KEGG) functional annotation and enrichment analysis were performed for DEGs.
RESULTS: T2DM-4w group vs. NG, T2DM-8w group vs. NG, and T2DM-12w group vs. NG detected 519 (251 up-regulated and 268 down-regulated), 459 (342 up-regulated and 117 down-regulated) and 328 (255 up-regulated and 73 down-regulated) DEGs, respectively. 103 key genes of sustained changes in the supraspinatus tendon following induction of diabetes, which are the first identified biomarkers of the supraspinatus tendon as it progresses through the course of diabetes.The GO analysis results showed that the most significant enrichment in biological processes was calcium ion transmembrane import into cytosol (3 DEGs). The most significant enrichment in cellular component was extracellular matrix (9 DEGs). The most significant enrichment in molecular function was glutamate-gated calcium ion channel activity (3 DEGs). The results of KEGG pathway enrichment analysis showed that there were 17 major pathways (p < 0.05) that diabetes affected supratinusculus tendinopathy, including cAMP signaling pathway and Calcium signaling pathway.
CONCLUSIONS: Transcriptomics reveals dynamic changes in the\"gene profiles\"of rat supraspinatus tendon at three different time points after diabetes induction. The 103 DEGs identified in this study may provide potential molecular markers for exploring the pathogenesis of diabetic tendinopathy, and the 17 major pathways enriched in KEGG may provide new ideas for exploring the pathogenesis of diabetic tendinopathy.

BACKGROUND: Rotator cuff tendinopathy (RCT) is a widespread musculoskeletal disorder and a primary cause of shoulder pain and limited function. The resulting pain and limited functionality have a detrimental impact on the overall quality of life. The purpose of this study was to perform a systematic review of the effects of extracorporeal shock wave therapy (ESWT) for RCT.
METHODS: The literature search was conducted on the following databases from inception to February 20, 2024: PubMed, Web of Science, the Cochrane Library, Scopus, MEDLINE, EMBASE, EBSCO, and China National Knowledge Infrastructure (CNKI) were checked to identify the potential studies exploring the effect of ESWT for the treatment of Rotator cuff tendinopathy (Calcification or non-calcification), control group for sham, other treatments (including placebo), without restriction of date, language. Two researchers independently screened literature, extracted data, evaluated the risk of bias in the included studies, and performed meta-analysis using RevMan 5.3 software.
RESULTS: A total of 16 RCTs with 1093 patients were included. The results showed that compared with the control group, ESWT for pain score Visual Analogue Scale/Score (VAS) (SMD = -1.95, 95% CI -2.47, -1.41, P < 0.00001), function score Constant-Murley score (CMS) (SMD = 1.30, 95% CI 0.67, 1.92, P < 0.00001), University of California Los Angeles score (UCLA) (SMD = 2.69, 95% CI 1.64, 3.74, P < 0.00001), American Shoulder and Elbow Surgeons form (ASES) (SMD = 1.29, 95% CI 0.93, 1.65, P < 0.00001), Range of motion (ROM) External rotation (SMD = 1.00, 95% CI 0.29, 1.72, P = 0.02), Total effective rate (TER) (OR = 3.64, 95% CI 1.85, 7.14, P = 0.0002), the differences in the above results were statistically significant. But ROM-Abduction (SMD = 0.72, 95% CI -0.22, 1.66, P = 0.13), the difference was not statistically significant.
CONCLUSIONS: Currently limited evidence suggests that, compared with the control group, ESWT can provide better pain relief, functional recovery, and maintenance of function in patients with RCT.

Tendinopathy is a prevalent condition in orthopedics patients, exerting a profound impact on tendon functionality. However, its underlying mechanism remains elusive and the efficacy of pharmacological interventions continues to be suboptimal. Verapamil is a clinically used medicine with anti-inflammation and antioxidant functions. This investigation aimed to elucidate the impact of verapamil in tendinopathy and the underlying mechanisms through which verapamil ameliorates the severity of tendinopathy. In in vitro experiments, primary tenocytes were exposed to interleukin-1 beta (IL-1β) along with verapamil at a concentration of 5 μM. In addition, an in vivo rat tendinopathy model was induced through the localized injection of collagenase into the Achilles tendons of rats, and verapamil was injected into these tendons at a concentration of 5 μM. The in vitro findings highlighted the remarkable ability of verapamil to attenuate extracellular matrix degradation and apoptosis triggered by inflammation in tenocytes stimulated by IL-1β. Furthermore, verapamil was observed to significantly suppress the inflammation-related MAPK/NFκB pathway. Subsequent investigations revealed that verapamil exerts a remediating effect on mitochondrial dysfunction, which was achieved through activation of the Nrf2/HO-1 pathway. Nevertheless, the protective effect of verapamil was nullified with the utilization of the Nrf2 inhibitor ML385. In summary, the in vivo and in vitro results indicate that the administration of verapamil profoundly mitigates the severity of tendinopathy through suppression of inflammation and activation of the Nrf2/HO-1 pathway. These findings suggest that verapamil is a promising therapeutic agent for the treatment of tendinopathy, deserving further and expanded research.

There is no mouse model of patellar tendinopathy. This study aimed to establish a mouse inflammatory and degenerative patellar tendon injury model, which will facilitate research on patellar tendinopathy using advanced molecular tools including transgenic models. Collagenase at different doses (low dose (LD), medium dose (MD), high dose (HD)) or saline was injected over the mouse patellar tendon. At weeks 1, 2, 4, and 8 post-injection, the tendons were harvested for histology and further examined by micro-computed tomography (microCT) imaging at week 8. The optimal dose group and the saline group were further evaluated by immunohistochemical staining, gait pattern, and biomechanical properties. The histopathological score increased dose-dependently post-collagenase injection. Ectopic mineralization was observed and increased with collagenase dose. The LD group was selected for further analysis. The expression of IL-10, TNF-α, and MMP-1 significantly increased post-injection. The changes of limb idleness index (ΔLII) compared to preinjury state were significantly higher, while the ultimate load, stiffness, ultimate stress, and maximum Young\'s modulus were significantly lower in the LD group compared to the saline group. A mouse inflammatory degenerative model of patellar tendon injury resembling tendinopathy was established as indicated by the dose-dependent increase in tendon histopathology, ectopic calcification, decrease in biomechanical properties, and pain-associated gait changes.

BACKGROUND: Calcific insertional Achilles tendinopathy(CIAT) with Haglund deformity is a type of recalcitrant tendinopathy. The necessity of concomitant removal of Haglund deformity during CIAT treatment is controversial. The present study aimed to evaluate the functional outcomes between Haglund resection and Haglund non-resection in the treatment of CIAT with Haglund deformity.
METHODS: A retrospective study included 29 patients who were underwent Achilles tendon debridement, bursal excision, and subsequent tendon reattachment.for CIAT with Haglund deformity. All patients were divided into 2 groups according to Haglund resection (resection group, n = 16) and Haglund non-resection (non-resection group, n = 13) using the parallel line method on lateral calcaneal X ray after surgery. Patients were evaluated in terms of the American Orthopedic Foot and Ankle Society (AOFAS), Visual Analog Scale (VAS) and Victorian Institute of Sports Assessment-Achilles (VISA-A) scores and the mean time of activities of daily living (ADL). Anatomy changes included the Fowler-Philip angle, calcaneal pitch angle and Achilles tendon force arm were measured with radiography preoperatively and postoperatively.
RESULTS: Both groups exhibited a significant increase in AOFAS, VAS and VISA-A scores after surgery. There were no significant differences between the resection group and the non-resection group for the AOFAS (92.38 ± 5.7 vs. 93.15 ± 12.17; P = 0.82), VAS (0.5 ± 0.52 vs. 0.61 ± 0.87; P = 0.66) and VISA-A questionnaire (82.56 ± 13.46 vs. 74.92 ± 16.4; P = 0.18) at the latest follow-up. The mean time of ADL in the non-resection group was significantly faster compared to that of the resection group (8.15 ± 2.51 weeks vs. 11.31 ± 4.06 weeks, P = 0.02). The Fowler-Philip angle of the resection group decreased from 55.55° ± 12.34° preoperatively to 44.52° ± 10.24° at the latest follow-up (P = 0.001). The Fowler-Philip angle of the non-resection group decreased from 54.38° ± 8.41° preoperatively to 46.52° ± 8.02° at the latest follow-up (P = 0.016). The calcaneal pitch angle of the resection group increased from 22.76° ± 5.37° preoperatively to 25.98° ± 6. 4° at the latest follow-up (P = 0.018). The Achilles tendon force arm of the resection group decreased from 178.50 mm ± 5.37 mm preoperatively to 173.90 mm ± 8.07 mm at the latest follow-up (P = 0.018).
CONCLUSIONS: Resection or non-resection of the posterosuperior calcaneal tuberosity for CIAT with Haglund deformity would both provide satisfactory functional outcomes. Haglund non-resection may expedite patients\' return to their daily activities, suggesting a Haglund deformity resection may be unnecessary in the surgical treatment for CIAT with Haglund deformity.

UNASSIGNED: Treatment options for calcific tendinitis (CT) of the shoulder remain controversial. A consensus for an operative indication for this condition is lacking.
UNASSIGNED: To compare nonoperative versus operative treatment for shoulder CT and analyze factors affecting the prognosis after treatment.
UNASSIGNED: Cohort study; Level of evidence, 3.
UNASSIGNED: A total of 180 patients diagnosed with symptomatic CT between January 2017 and September 2021 were evaluated in this retrospective cohort study. There were 103 patients treated nonoperatively at our institution, which included the use of nonsteroidal anti-inflammatory drugs, acupuncture, steroid injections, extracorporeal shock wave therapy, and ultrasound-guided needle aspiration/percutaneous irrigation. However, 77 patients were treated with arthroscopic surgery after 6 months of failed nonoperative treatment. The visual analog scale (VAS) for pain, the Constant-Murley score, and imaging were used to assess and evaluate outcomes. Descriptive data, functional outcomes, and imaging findings were compared between the operative and nonoperative groups before and after propensity score matching. Additionally, prognostic factors including calcium deposit size, tendon infiltration by calcium deposits, involvement of single or multiple tendons, and occurrence of rotator cuff tears were analyzed by comparing the groups to determine their effect on treatment options and recovery.
UNASSIGNED: Magnetic resonance imaging showed that the supraspinatus tendon (66.7%) was most commonly involved, followed by the infraspinatus (42.8%) and subscapularis (21.1%) tendons. Tendon infiltration by calcium deposits was observed in 84.4% of the patients, and rotator cuff tears occurred in 30.0% of the patients. After propensity score matching, there was no significant difference in changes in the Constant-Murley score (48.1 ± 25.4 vs 49.0 ± 22.8, respectively; P = .950) and VAS score (4.9 ± 2.3 vs 4.5 ± 1.9, respectively; P = .860) between the operative and nonoperative groups at the final follow-up. However, for patients with shoulder CT and without rotator cuff tears, there was a significant difference in changes in the Constant-Murley score (52.93 ± 25.18 vs 42.13 ± 22.35, respectively; P = .012) and VAS score (5.21 ± 2.06 vs 3.81 ± 1.98, respectively; P < .001) between the operative and nonoperative groups, but the recovery time in the operative group was longer than that in the nonoperative group (86.92 ± 138.56 vs 30.42 ± 54.97 days, respectively; P = .016). The results also showed that calcium deposit size, involvement of multiple tendons, and tendon infiltration by calcium deposits did not affect the recovery time after treatment. The survival analysis showed that rotator cuff tears affected the complete recovery of shoulder function.
UNASSIGNED: This study demonstrated no significant difference between nonoperative and operative treatment for patients with shoulder CT, on the whole. However, for patients with shoulder CT and without rotator cuff tears, the effect of operative treatment was better than that of nonoperative treatment; yet, operative treatment was shown to prolong the recovery time. Calcium deposit size, tendon infiltration by calcium deposits, and involvement of multiple tendons did not correlate with recovery time or the recovery of function. A rotator cuff tear was the only factor affecting the complete recovery of shoulder function.