Aims. The purpose of this study was to evaluate the in vitro effects of apocynin, an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase (NOX) and a downregulator of intracellular reactive oxygen species (ROS), on high glucose-induced oxidative stress on tenocytes. Methods. Tenocytes from normal Sprague-Dawley rats were cultured in both control and high-glucose conditions. Apocynin was added at cell seeding, dividing the tenocytes into four groups: the control group; regular glucose with apocynin (RG apo+); high glucose with apocynin (HG apo+); and high glucose without apocynin (HG apo–). Reactive oxygen species production, cell proliferation, apoptosis and messenger RNA (mRNA) expression of NOX1 and 4, and interleukin-6 (IL-6) were determined in vitro. Results. Expression of NOX1, NOX4, and IL-6 mRNA in the HG groups was significantly higher compared with that in the RG groups, and NOX1, NOX4, and IL-6 mRNA expression in the HG apo+ group was significantly lower compared with that in the HG apo– group. Cell proliferation in the RG apo+ group was significantly higher than in the control group and was also significantly higher in the HG apo+ group than in the HG apo– group. Both the ROS accumulation and the amounts of apoptotic cells in the HG groups were greater than those in the RG groups and were significantly less in the HG apo+ group than in the HG apo– group. Conclusion. Apocynin reduced ROS production and cell death via NOX inhibition in high-glucose conditions. Apocynin is therefore a potential prodrug in the treatment of diabetic tendinopathy. Cite this article:Bone Joint Res 2020;9(1):23–28

In recent years, the plantaris tendon has been implicated in the development of chronic painful mid-portion Achilles tendinopathy. In some cases, a thickened plantaris tendon is closely associated with the Achilles tendon, and surgical excision of the plantaris tendon has been reported to be curative in patients who have not derived benefit following conservative treatment and surgical interventions. The aim of this review is to outline the basic aspects of, and the recent research findings, related to the plantaris tendon, covering anatomical and clinical studies including those dealing with histology, imaging and treatment. Cite this article: Bone Joint J 2016;98-B:1312–19

Objectives. The aim of this study was to investigate the effect of hyperglycaemia on oxidative stress markers and inflammatory and matrix gene expression within tendons of normal and diabetic rats and to give insights into the processes involved in tendinopathy. Methods. Using tenocytes from normal Sprague-Dawley rats, cultured both in control and high glucose conditions, reactive oxygen species (ROS) production, cell proliferation, messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, interleukin-6 (IL-6), matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-1 and -2 and type I and III collagens were determined after 48 and 72 hours in vitro. In an in vivo study, using diabetic rats and controls, NOX1 and 4 expressions in Achilles tendon were also determined. Results. In tenocyte cultures grown under high glucose conditions, gene expressions of NOX1, MMP-2, TIMP-1 and -2 after 48 and 72 hours, NOX4 after 48 hours and IL-6, type III collagen and TIMP-2 after 72 hours were significantly higher than those in control cultures grown under control glucose conditions. Type I collagen expression was significantly lower after 72 hours. ROS accumulation was significantly higher after 48 hours, and cell proliferation after 48 and 72 hours was significantly lower in high glucose than in control glucose conditions. In the diabetic rat model, NOX1 expression within the Achilles tendon was also significantly increased. Conclusion. This study suggests that high glucose conditions upregulate the expression of mRNA for NOX1 and IL-6 and the production of ROS. Moreover, high glucose conditions induce an abnormal tendon matrix expression pattern of type I collagen and a decrease in the proliferation of rat tenocytes. Cite this article: Y. Ueda, A. Inui, Y. Mifune, R. Sakata, T. Muto, Y. Harada, F. Takase, T. Kataoka, T. Kokubu, R. Kuroda. The effects of high glucose condition on rat tenocytes in vitro and rat Achilles tendon in vivo. Bone Joint Res 2018;7:362–372. DOI: 10.1302/2046-3758.75.BJR-2017-0126.R2

Aims. The traditional transosseus flexor hallucis longus (FHL) tendon transfer for patients with Achilles tendinopathy requires two incisions to harvest a long tendon graft. The use of a bio-tenodesis screw enables a short graft to be used and is less invasive, but lacks supporting evidence about its biomechanical behaviour. We aimed, in this study, to compare the strength of the traditional transosseus tendon-to-tendon fixation with tendon-to-bone fixation using a tenodesis screw, in cyclical loading and ultimate load testing. Materials and Methods. Tendon grafts were undertaken in 24 paired lower-leg specimens and randomly assigned in two groups using fixation with a transosseus suture (suture group) or a tenodesis screw (screw group). The biomechanical behaviour was evaluated using cyclical and ultimate loading tests. The Student’s t-test was performed to assess statistically significant differences in bone mineral density (BMD), displacement, the slope of the load-displacement curves, and load to failure. Results. The screw group showed less displacement (loosening) during cyclical loading, which was significant during 300, 500, 600, 700, 800, 900, and 1000 cycles (p < 0.05: other cycles: 0.079 < p < 0.402). Compared with the suture group, the screw group had higher mean ultimate load values (133.6 N, . sd. 73.5 vs 110.1 N,. sd. 46.2; p = 0.416). Conclusion. Fixation of the FHL tendon with a tenodesis screw enables a less invasive procedure to be undertaken and shows similar biomechanical behaviour and primary strength compared with fixation using a transosseus suture. Cite this article: Bone Joint J 2018;100-B:1175–81

The October 2014 Research Roundup. 360 . looks at: unpicking syndesmotic injuries: CT scans evaluated; surgical scrub suits and sterility in theatre; continuous passive motion and knee injuries; whether pain at night is melatonin related;venous thromboembolic disease following spinal surgery; clots in lower limb plasters; immune-competent cells in Achilles tendinopathy; and infection in orthopaedics

Tendinopathy is a debilitating musculoskeletal condition which can cause significant pain and lead to complete rupture of the tendon, which often requires surgical repair. Due in part to the large spectrum of tendon pathologies, these disorders continue to be a clinical challenge. Animal models are often used in this field of research as they offer an attractive framework to examine the cascade of processes that occur throughout both tendon pathology and repair. This review discusses the structural, mechanical, and biological changes that occur throughout tendon pathology in animal models, as well as strategies for the improvement of tendon healing. Cite this article: Bone Joint Res 2014;3:193–202

The February 2014 Foot & Ankle Roundup. 360 . looks at: optimal medial malleolar fixation; resurfacing in the talus; predicting outcome in mobility ankles; whether mal-aligned ankles can be successfully replaced; cartilage colonisation in bipolar ankle grafts; CTs and proof of fusion; recalcitrant Achilles tendinopathy; and recurrent fifth metatarsal stress fractures

The use of ultrasound in the diagnosis and management of disorders of the tendo Achillis is discussed. Some of the pathological processes which occur in Achilles tendinopathy can be identified by ultrasound, which may also be used to direct local treatment

The April 2012 Knee Roundup. 360 . looks at the torn ACL, ACL reconstruction, the risk of ACL rupture, the benefit of warm-ups before exercise, glucosamine and tibiofemoral osteoarthritis, sensitisation and sporting tendinopathy, pain relief after TKR, the long-term results of the Genesis I, the gender specific recovery times after TKR, and the accuracy of the orthopaedic eyeball

The April 2013 Foot & Ankle Roundup. 360 . looks at: whether arthroscopic arthrodesis is advantageous; osteochondral autografts; suture button associated fractures; an ultrasound solution to Achilles tendinopathy; the safety of the tendo Achilles in men; charcot and antibiotic-coated nails; and botox and Policeman’s Heel

Aims

Myokine developmental endothelial locus-1 (DEL-1) has been documented to alleviate inflammation and endoplasmic reticulum (ER) stress in various cell types. However, the effects of DEL-1 on inflammation, ER stress, and apoptosis in tenocytes remain unclear.

Objectives . The effects of disease progression and common tendinopathy treatments on the tissue characteristics of human rotator cuff tendons have not previously been evaluated in detail owing to a lack of suitable sampling techniques. This study evaluated the structural characteristics of torn human supraspinatus tendons across the full disease spectrum, and the short-term effects of subacromial corticosteroid injections (SCIs) and subacromial decompression (SAD) surgery on these structural characteristics. . Methods . Samples were collected inter-operatively from supraspinatus tendons containing small, medium, large and massive full thickness tears (n = 33). Using a novel minimally invasive biopsy technique, paired samples were also collected from supraspinatus tendons containing partial thickness tears either before and seven weeks after subacromial SCI (n = 11), or before and seven weeks after SAD surgery (n = 14). Macroscopically normal subscapularis tendons of older patients (n = 5, mean age = 74.6 years) and supraspinatus tendons of younger patients (n = 16, mean age = 23.3) served as controls. Ultra- and micro-structural characteristics were assessed using atomic force microscopy and polarised light microscopy respectively. . Results. Significant structural differences existed between torn and control groups. Differences were identifiable early in the disease spectrum, and increased with increasing tear size. Neither SCI nor SAD surgery altered the structural properties of partially torn tendons seven weeks after treatment. . Conclusions . These findings may suggest the need for early clinical intervention strategies for torn rotator cuff tendons in order to prevent further degeneration of the tissue as tear size increases. Further work is required to establish the long-term abilities of SCI and SAD to prevent, and even reverse, such degeneration. Cite this article: Bone Joint Res 2014;3:252–61

Aims

Mechanical impingement of the iliopsoas (IP) tendon accounts for 2% to 6% of persistent postoperative pain after total hip arthroplasty (THA). The most common initiator is anterior acetabular component protrusion, where the anterior margin is not covered by anterior acetabular wall. A CT scan can be used to identify and measure this overhang; however, no threshold exists for determining symptomatic anterior IP impingement due to overhang. A case-control study was conducted in which CT scan measurements were used to define a threshold that differentiates patients with IP impingement from asymptomatic patients after THA.

The August 2012 Knee Roundup. 360. looks at: meniscal defects and a polyurethane scaffold; which is best between a single or double bundle; OA of the knee; how to resolve anterior knee pain; whether yoga can be bad for your menisci; metal ions in the serum; whether ACI is any good; the ACL; whether hyaluronic acid delays collagen degradation; and hyaluronan and patellar tendinopathy

Among the variety of differential diagnoses for chronic patellar tendinopathy, isolated tuberculosis is extremely rare. We report such a case, without any evident primary contiguous or distant focus, in a 31-year-old immunocompetent male

The April 2012 Foot & Ankle Roundup. 360 . looks at injecting the tendon sheath, total ankle replacement, heterotopic ossification, replacement or arthrodesis, achilles tendinopathy, healing of the torn Achilles, grafting of the calcaneal bone cyst, avulsion fractures in athletes, percutaneous distal osteotomy for bunionette formation, and repairing the torn tibiofibular syndesmosis

The December 2022 Foot & Ankle Roundup³⁶⁰ looks at: Evans calcaneal osteotomy and multiplanar correction in flat foot deformity; Inflammatory biomarkers in tibialis posterior tendon dysfunction; Takedown of ankle fusions and conversion to total ankle arthroplasty; Surgical incision closure with three different materials; Absorbable sutures are not inferior to nonabsorbable sutures for tendo Achilles repair; Zadek’s osteotomy is a reliable technique for treating Haglund’s syndrome; How to best assess patient limitations after acute Achilles tendon injury; Advances in the management of infected nonunion of the foot and ankle.

Objectives. To investigate the appropriate dose and interval for the administration of triamcinolone acetonide (TA) in treating tendinopathy to avoid adverse effects such as tendon degeneration and rupture. Methods. Human rotator cuff-derived cells were cultured using three media: regular medium (control), regular medium with 0.1 mg/mL of TA (low TA group), and with 1.0 mg/mL of TA (high TA group). The cell morphology, apoptosis, and viability were assessed at designated time points. Results. In the low TA group, the cells became flattened and polygonal at seven days then returned to normal at 21 days. The cell apoptosis ratio and messenger ribonucleic acid expression of caspase-3, 7, 8, and 9 increased, and viability was reduced in the low and high groups at seven days. In the low TA group, apoptosis and viability returned to normal at 21 days, however, in the high TA group, the cell morphology, apoptosis ratio, caspase-3, 7, 8, and 9 and viability did not return by day 21. Re-administration was performed in the low TA group at 7-, 14-, and 21-day intervals, and cell viability did not return to the control level at the 7- and 14-day intervals. Conclusion. A 0.1 mg/mL dose of TA temporarily decreased cell viability and increased cell apoptosis, which was recovered at 21 days, however, 1 mg/mL of TA caused irreversible damage to cell morphology and viability. An interval > three weeks was needed to safely re-administer TA. These findings may help determine the appropriate dose and interval for TA injection therapy. Cite this article: Bone Joint Res 2014;3:328–34

Tendon is a bradytrophic and hypovascular tissue, hence, healing remains a major challenge. The molecular key events involved in successful repair have to be unravelled to develop novel strategies that reduce the risk of unfavourable outcomes such as non-healing, adhesion formation, and scarring. This review will consider the diverse pathophysiological features of tendon-derived cells that lead to failed healing, including misrouted differentiation (e.g. de- or transdifferentiation) and premature cell senescence, as well as the loss of functional progenitors. Many of these features can be attributed to disturbed cell-extracellular matrix (ECM) or unbalanced soluble mediators involving not only resident tendon cells, but also the cross-talk with immigrating immune cell populations. Unrestrained post-traumatic inflammation could hinder successful healing. Pro-angiogenic mediators trigger hypervascularization and lead to persistence of an immature repair tissue, which does not provide sufficient mechano-competence. Tendon repair tissue needs to achieve an ECM composition, structure, strength, and stiffness that resembles the undamaged highly hierarchically ordered tendon ECM. Adequate mechano-sensation and -transduction by tendon cells orchestrate ECM synthesis, stabilization by cross-linking, and remodelling as a prerequisite for the adaptation to the increased mechanical challenges during healing. Lastly, this review will discuss, from the cell biological point of view, possible optimization strategies for augmenting Achilles tendon (AT) healing outcomes, including adapted mechanostimulation and novel approaches by restraining neoangiogenesis, modifying stem cell niche parameters, tissue engineering, the modulation of the inflammatory cells, and the application of stimulatory factors.

Cite this article: Bone Joint Res 2022;11(8):561–574.

Peri-tendinous injection of local anaesthetic, both alone and in combination with corticosteroids, is commonly performed in the treatment of tendinopathies. Previous studies have shown that local anaesthetics and corticosteroids are chondrotoxic, but their effect on tenocytes remains unknown. We compared the effects of lidocaine and ropivacaine, alone or combined with dexamethasone, on the viability of cultured bovine tenocytes. Tenocytes were exposed to ten different conditions: 1) normal saline; 2) 1% lidocaine; 3) 2% lidocaine; 4) 0.2% ropivacaine; 5) 0.5% ropivacaine; 6) dexamethasone (dex); 7) 1% lidocaine+dex; 8) 2% lidocaine+dex; 9) 0.2% ropivacaine+dex; and 10) 0.5% ropivacaine+dex, for 30 minutes. After a 24-hour recovery period, the viability of the tenocytes was quantified using the CellTiter-Glo viability assay and fluorescence-activated cell sorting (FACS) for live/dead cell counts. A 30-minute exposure to lidocaine alone was significantly toxic to the tenocytes in a dose-dependent manner, but a 30-minute exposure to ropivacaine or dexamethasone alone was not significantly toxic. Dexamethasone potentiated ropivacaine tenocyte toxicity at higher doses of ropivacaine, but did not potentiate lidocaine tenocyte toxicity. As seen in other cell types, lidocaine has a dose-dependent toxicity to tenocytes but ropivacaine is not significantly toxic. Although dexamethasone alone is not toxic, its combination with 0.5% ropivacaine significantly increased its toxicity to tenocytes. These findings might be relevant to clinical practice and warrant further investigation