Adenylate cyclase activates the cAMP signalling pathway to enhance platelet-rich plasma-treated Achilles tendon disease, a theoretical bioinformatics-based study.

The effectiveness of platelet-rich plasma (PRP) for the treatment of Achilles tendon disorders still needs to be evaluated through a series of prospective studies, but genomic analysis can reveal the existence of complementary PRP treatment options. Based on the 96 platelet activation-related genes in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, we performed Gene Ontology functional enrichment analysis and KEGG enrichment analysis, pathway correlation analysis, and enrichment mapping to determine the enrichment results of the gene set enrichment analysis and found that the cAMP signalling pathway may be the key to enhancing the effectiveness of PRP treatment. The cAMP signalling pathway interacts with the Rap1 signalling pathway and cGMP-PKG signalling pathway to mediate the entire pathophysiological process of Achilles tendon disease. Moreover, ADCY1-9 may be the key to the activation of the cAMP signalling network. Further based on the data in the Gene Expression Omnibus database, it was found that ADCY4 and ADCY7 may be the players that play a major role, associated with the STAT4-ADCY4-LAMA5 axis and the GRbeta-ADCY7-SEMA3C axis, which is expected to be a complementary target for enhancing the efficacy of PRP in the treatment of Achilles tendon disease.

Characterization of Equine Chronic Tendon Lesions in Low- and High-Field Magnetic Resonance Imaging.

In equine medicine, experience regarding MRI of chronic tendon lesions is limited, and evidence on the suitability of different sequences in 3 T high-field MRI is scarce. Therefore, macroscopically healthy and altered tendons were examined by histology and in 0.27 T low- and 3 T high-field MRI, focusing on T1-weighted (T1w) sequences to visualize chronic lesions. In high-field MRI, tendons were positioned parallel (horizontal) and perpendicular (vertical) to the magnetic field, acknowledging the possible impact of the magic angle effect. The images were evaluated qualitatively and signal intensities were measured for quantitative analysis. Qualitative evaluation was consistent with the quantitative results, yet there were differences in lesion detection between the sequences. The low-field T1w GRE sequence and high-field T1w FLASH sequence with vertically positioned tendons displayed all tendon lesions. However, the horizontally scanned high-field T1w SE sequence failed to detect chronic tendon lesions. The agreement regarding tendon signal intensities was higher between high-field sequences scanned in the same orientation (horizontal or vertical) than between the same types of sequence (SE or FLASH), demonstrating the impact of tendon positioning. Vertical scanning was superior for diagnosis of the tendon lesions, suggesting that the magic angle effect plays a major role in detecting chronic tendon disease.

Therapeutic effects of asperosaponin VI in rabbit tendon disease.

Introduction: This study explored the effects and molecular mechanisms of asperosaponin VI in tendon disease. Methods: Forty-eight purebred adult male New Zealand white rabbits were randomly divided into the normal group (normal, n = 8); saline group (saline, n = 8) and prostaglandin E2 group (n = 32), which was further divided into four subgroups that were treated with asperosaponin VI doses of 0 mg/kg (model, n = 8), 10 mg/kg (10, n = 8), 20 mg/kg (20, n = 8) and 40 mg/kg (40, n = 8). The expression levels of matrix metallopeptidase 1 (MMP1), metallopeptidase inhibitor 1 (TIMP1), transforming growth factor beta 1 (TGFB1), serpin family E member 1 (SERPINE1), collagen Ⅰ (COL1), collagen Ⅲ (COL3) and tenomodulin (TNMD) in Achilles tendon tissue were determined through Western blot analysis. The histopathological changes in tendon tissue were observed by using Masson staining and haematoxylin-eosin staining. Results: The expression levels of MMP1, TIMP1 and COL3 were higher and those of TGFB1, SERPINE1, COL1 and TNMD were lower in the 0 mg/kg group than in the normal group (P < 0.05). Compared with those in the 0 mg/kg group, the levels of MMP1 were lower in the 20 and 40 mg/kg groups. Compared with those in the 0 mg/kg group, the levels of TIMP1 were lower and the levels of TGFB1, COL1 and TNMD were higher in the 10, 20 and 40 mg/kg groups. In addition, compared with those in other groups, the levels of SERPINE1 in the 40 mg/kg group were significantly higher and the levels of COL3 in the 10 and 20 mg/kg groups were significantly lower (P < 0.05). Fibrous tissue arrangements and structures in the 40 mg/kg group were similar to those in the control group. Conclusion: The effects of asperosaponin VI on injured tendons mainly involve eliminating inflammation, restoring balance to extracellular matrix collagen metabolism and inducing tendon cell proliferation. Asperosaponin VI is likely to be an ideal drug for the prevention and treatment of tendon disease.

Mesenchymal Stromal Cells Adapt to Chronic Tendon Disease Environment with an Initial Reduction in Matrix Remodeling.

Tendon lesions are common sporting injuries in humans and horses alike. The healing process of acute tendon lesions frequently results in fibrosis and chronic disease. In horses, local mesenchymal stromal cell (MSC) injection is an accepted therapeutic strategy with positive influence on acute lesions. Concerning the use of MSCs in chronic tendon disease, data are scarce but suggest less therapeutic benefit. However, it has been shown that MSCs can have a positive effect on fibrotic tissue. Therefore, we aimed to elucidate the interplay of MSCs and healthy or chronically diseased tendon matrix. Equine MSCs were cultured either as cell aggregates or on scaffolds from healthy or diseased equine tendons. Higher expression of tendon-related matrix genes and tissue inhibitors of metalloproteinases (TIMPs) was found in aggregate cultures. However, the tenogenic transcription factor scleraxis was upregulated on healthy and diseased tendon scaffolds. Matrix metalloproteinase (MMPs) expression and activity were highest in healthy scaffold cultures but showed a strong transient decrease in diseased scaffold cultures. The release of glycosaminoglycan and collagen was also higher in scaffold cultures, even more so in those with tendon disease. This study points to an early suppression of MSC matrix remodeling activity by diseased tendon matrix, while tenogenic differentiation remained unaffected.

The attempt of spontaneous repair of rotator cuff tear: The role of periostin.

The development of a periostin-rich microenvironment in areas associated with insult, orchestrating pathways of repair and rebuilding, is documented. Literature lacks information regarding the presence of periostin in the context of rotator cuff tear (RCT). 55 consecutive patients with RCT were enrolled. Immunohistochemical periostin detection was performed on tissue samples excised from tear margins. Our study documented the presence of periostin in the margins of RCT. It is plausible that, when a tear occurs, multiple stimuli, both mechanical and inflammatory, lead to the development of a periostin-rich microenvironment as an attempt to tendon healing.

Carbon-14 bomb pulse dating shows that tendinopathy is preceded by years of abnormally high collagen turnover.

Tendons are essential weight-bearing structures that are often affected by tendinopathy, which leads to pain and impaired mobility. In healthy Achilles tendons, no significant renewal of the weight-bearing collagen matrix seems to occur during adult life, but tendinopathy may lead to increased turnover. The carbon-14 ([14C]) bomb pulse method was used to measure lifelong replacement rates of collagen in tendinopathic and healthy Achilles tendons (tendinopathic: n = 25, born 1937-1972. Healthy: n = 10, born 1929-1966). As expected, the healthy tendon collagen had not been replaced during adulthood, but in tendinopathic tendon, a substantial renewal had occurred. Modeling of the [14C] data suggested that one half of the collagen in tendinopathic matrix had undergone continuous slow turnover for years before the presentation of symptoms. This finding allows for a new concept in tendon pathogenesis because it suggests that either the symptoms of tendinopathy represent a late phase of a very prolonged disease process, or an abnormally high collagen exchange could be a risk factor for tendon disorders rather than being a result of disease.-Heinemeier, K. M., Schjerling, P., Øhlenschlæger, T. F., Eismark, C., Olsen, J., Kjær, M. Carbon-14 bomb pulse dating shows that tendinopathy is preceded by years of abnormally high collagen turnover.

Clinical features of patients diagnosed with degenerative rotator cuff tendon disease: a 6-month prospective-definitive clinical study from turkey.

[Purpose] In rotator cuff tendon disease (RCTD), anamnesis is as important as clinical findings and anatomic/radio diagnostic examination. This study aimed to investigate the clinical features of patients diagnosed with RCTD using clinical and radiological methods between March 2015 and August 2015 at Malatya Research and Training Hospital Physical Medicine and Rehabilitation department. [Subjects and Methods] The study included 178 patients who were diagnosed with RCTD (128 females and 50 males). A questionnaire comprising 33 questions was given to each patient. [Results] Eighty-eight of the patients (49.9%) had an involvement on their right side, eighty-four (47.1%) had an involvement on their left side, and 6 had bilateral involvement. Mean visual analog scale (VAS) score was found to be statistically significant in favor of female patients. A statistically significant correlation was found between educational status and VAS. The body mass index (BMI) of the female patients was found to be higher than that of the male patients. Statistically significant correlation between doing risky work and gender showed that males were at a higher risk. [Conclusion] RCDT is more seen in people who have high BMI and are at their 50s. Pain complaint and BMI were found higher in female patients. DM, thyroid and cardiac diseases were seen more in the patients who are diagnosed with RCTD relative to the healthy population.

Ultrasound-guided procedures around the wrist and hand: how to do.

Ultrasound has emerged as a low-cost, radiation-free and effective imaging technique to detect joint abnormalities and to guide percutaneous procedures. Being superficial, wrist and hand tendons and joints represent a good target to perform such procedures using ultrasound guidance. This kind of approach allows for a clear and real-time visualization of the needles during their whole path. In this setting, the knowledge of technical aspects and tips is essential to act in the most accurate way on target tissues that can be as small as a few millimetres. The aim of this review is to summarize the local treatments of inflammatory and degenerative disease described in literature (such as treatment of De Quervain's tenosynovitis, trigger finger, trapezio-metacarpal joint osteoarthritis, etc.), emphasizing precautions and tricks based on day-by-day experience that may help to improve the outcome of percutaneous ultrasound-guided procedures around the wrist and hand.

Investigating the efficacy of amnion-derived compared with bone marrow-derived mesenchymal stromal cells in equine tendon and ligament injuries.

BACKGROUND AIMS: This is the first study to compare the treatment of horse tendon and ligament injuries with the use of mesenchymal stromal cells (MSCs) obtained from two different sources: amniotic membrane (AMSCs) and bone marrow (BM-MSCs). The objective was to prove the ability of AMSCs to exert beneficial effects in vivo. METHODS: Five million allogeneic frozen-thawed AMSCs or autologous fresh BM-MSCs were injected intralesionally in horses belonging to group A (51 horses) and group B (44 horses). The interval lesion/implantation was of 6-15 days for the AMSCs and 16-35 days for the BM-MSCs. Healing was assessed clinically and ultrasonographically. Follow-up was monitored for 2 further years from return to full work. RESULTS: No significant adverse effects after MSCs treatment were seen in any of the horses studied, independent of the type of stromal cell implanted. All animals belonging to group A resumed their activities between 4-5 months after treatment, whereas animals of group B resumed their activities after 4-12 months. The rate of re-injury in horses treated with AMSCs is lower (4.00%) compared with the average observed when horses were treated with BM-MSCs (23.08%). CONCLUSIONS: The possibility to inject allogeneic AMSCs in real time, before any ultrasonographic change occurs within the injured tendon and ligament, together with the higher plasticity and proliferative capacity of these cells compared with BM-MSCs, represents the main features of interest for this novel approach for the treatment of equine tendon diseases. An obvious active proliferative healing in the area injected with AMSCs makes these cells more effective than BM-MSCs.

Operative treatment of chronic irreparable Achilles tendon ruptures with large flexor hallucis longus tendon transfers.

BACKGROUND: Transfer of the flexor hallucis longus (FHL) tendon aims to restore function and relieve pain in chronic Achilles tendon (AT) disease. The goal of the present study was to investigate the clinical and radiographic outcomes of FHL transfer to the AT and to compare the transtendinous technique to the transosseous technique. We hypothesized that the type of technique would have a notable impact on outcome. METHODS: Forty patients (42 ankles) were retrospectively reviewed and divided into group 1 (transtendinous technique, 22 patients/24 ankles) and group 2 (transosseous technique, 18 patients/18 ankles). Outcome parameters included the American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot score, Victorian Institute of Sports Assessment-Achilles (VISA-A) score, Foot Function Index (FFI), and Short Form-36 (SF-36) scores. Magnetic resonance imaging of the lower leg was performed preoperatively to assess muscle quality and fatty infiltration. Postoperatively, isokinetic plantar flexion strength was assessed using a Con-Trex dynamometer. RESULTS: In group 1 (follow-up, 73 months; age, 52 years), the AOFAS score improved from 66 points to 89 points (P < .001) with average values for the VISA-A of 76 points, FFI-D pain 15%, and FFI-D function 22%. In group 2 (follow-up, 35 months; age, 56 years), the AOFAS score increased from 59 points to 85 points (P < .001) with mean values for the VISA-A 76 points, FFI-D pain 25%, and FFI-D function 24%. At follow-up, the average SF-36 score in group 1 was 66% and in group 2 was 77%. Isokinetic testing at 30 deg/s in group 1 revealed notable weakness in the operated ankle averaging 54.7 N·m (75% of normal), and in group 2 the average was 58.2 N·m (77% of normal). No statistically significant differences were found between the groups. CONCLUSION: The hypothesis was disproved. Both techniques for FHL transfer to AT, intratendinous and transosseous, provided good to excellent clinical and functional outcome in the treatment of irreparable AT disease. LEVEL OF EVIDENCE: Level III, retrospective comparative series.

Ultra-sonografia na avaliação das afeccões agudas do sistema músculo-esquelético: parte I: afecções não-traumáticas / Ultrasonographic assessment of acute musculoskeletal diseases: part I: non-traumatic lesions

A ultra-sonografia é um método eficaz na avaliação de afecções agudas acometendo o sistema músculo-esquelético, constituindo importante arma propedêutica nos serviços de atendimento de urgência. O ultra-som permite a avaliação de ampla variedade de lesões de origem não-traumática,tais como lesões infecciosas articulares ou extra-articulares, e a avaliação de lesões não-infecciosas, tais como doenças bursais e tendíneas agudas ou agudizadas. Será apresentada breve revisão das principais indicações do exame ultra-sonográfico, ilustrada com casos típicos provenientes de arquivo digital, sendo discutidos os achados fundamentais para a caracterização e o diagnóstico das afecções não-traumáticas mais freqüentes. Todos os casos apresentados procuraram o serviço de pronto-atendimento do nosso hospital devido a queixas agudas relacionadas ao sistema músculo-esquelético.

Ultrasonography is accurate in the evaluation of acute musculoskeletal injuries and became an important diagnostic method in the urgency department. Ultrasonography allows evaluation of diverse non-traumatic lesions, as infectious articular or extra-articular lesions, and non-infectious diseases, as acute tendon or bursaldiseases. This article review the role of sonographic assessment in the acute musculoskeletal setting, illustrated with cases from soft copy archives, discussing the main aspects of the mostcommon musculoskeletal complains in the urgency department.