Transcriptomic and Genetic Analyses Identify the Krüppel-Like Factor Dar1 as a New Regulator of Tube-Shaped Long Tendon Development

To ensure locomotion and body stability, the active role of muscle contractions relies on a stereotyped muscle pattern set in place during development. This muscle patterning requires a precise assembly of the muscle fibers with the skeleton via a specialized connective tissue, the tendon. Like in vertebrate limbs, Drosophila leg muscles make connections with specific long tendons that extend through different segments. During the leg disc development, cell precursors of long tendons rearrange and collectively migrate to form a tube-shaped structure. A specific developmental program underlies this unique feature of tendon-like cells in the Drosophila model. We provide for the first time a transcriptomic profile of leg tendon precursors through fluorescence-based cell sorting. From promising candidates, we identified the Krüppel-like factor Dar1 as a critical actor of leg tendon development. Specifically expressed in the leg tendon precursors, loss of dar1 disrupts actin-rich filopodia formation and tendon elongation. Our findings show that Dar1 acts downstream of Stripe and is required to set up the correct number of tendon progenitors.

A Simplified Method for Considering Achilles Tendon Curvature in the Assessment of Tendon Elongation

The consideration of the Achilles tendon (AT) curvature is crucial for the precise determination of AT length and strain. We previously established an ultrasound-kinematic-based method to quantify the curvature, using a line of reflective foil skin markers covering the AT from origin to insertion. The current study aimed to simplify the method by reducing the number of markers while maintaining high accuracy. Eleven participants walked (1.4 m/s) and ran (2.5, 3.5 m/s) on a treadmill, and the AT curvature was quantified using reflective foil markers aligned with the AT between the origin on the gastrocnemius myotendinous-junction (tracked by ultrasound) and a marker on the calcaneal insertion. Foil markers were then systematically removed, and the introduced error on the assessment of AT length and strain was calculated. We found a significant main effect of marker number on the measurement error of AT length and strain (p<0.001). Using more than 30% of the full marker-set for walking and 50% for running, the R2 of the AT length error saturated, corresponding to average errors of <0.1 mm and <0.15% strain. Therefore, a substantially reduced marker-set, associated with a marginal error, can be recommended for considering the AT curvature in the determination of AT length and strain.

Comparative Study of Biomechanical Properties between Needled Suture and Needleless Suture in Multi-Strand Tendon Graft Model

Objective: To compare the biomechanical properties of the Chinese finger (CF) suture, a needleless suture technique, with the baseball stitch (BS) suture, a needled suture technique, in a multi-strand model by using a 4-strand tendon model. Additionally, the BS was compared with the serial rolling hitch (RH), a locking needleless suture technique. Materials and Methods: 4-strand grafts, made from two 20-cm fresh porcine toe extensors, were used in all three groups. After the grafts were sutured, pretension was applied with a load of 100-N distraction force for five minutes. After the tendon elongation was measured before and after the pretension, the distraction force was continued until the constructed graft failed. Stress-strain relationship graphs were recorded by universal testing machine (UTM), distributing to the calculation of percentage on tendon elongation, stiffness, and load-to-failure. Results: The BS had significantly higher load of failure than the CF (p=0.001) but no significant difference when compared with the RH. Comparing between BS, CF, and RH, there were no significant difference in stiffness and percentage of tendon elongation. In modes of failure, there was evidence of knot slipping in CF in six of six cases and graft strangulation in RH in four of six cases. Conclusion: Multi-strand model BS, a needled suture, had a higher load to failure than CF, a needleless suture. Moreover, needleless sutures had serious modes of failure, which were knot slipping and strangulation of graft by the suture material. Therefore, needleless suture technique for multi-strand tendon graft preparation was not recommended. Keywords: Tendon preparation; Multi-Strand; Needled suture; Needleless suture; Chinese finger; Baseball stitch; Rolling Hitch; Biomechanical study; Graft elongation; Load to failure

Superior oblique split tendon elongation for Brown’s syndrome: Long-term outcomes

Purpose:To report the outcomes of superior oblique split tendon elongation in Brown’s syndrome.Methods:Charts of 17 consecutive Brown’s syndrome patients who underwent superior oblique split tendon elongation were reviewed and clinical data regarding preoperative, intraoperative, and postoperative data were collected.Results:About 17 eyes of 17 children with congenital Brown’s syndrome underwent superior oblique split tendon elongation between January 2012 and March 2020 by a single surgeon. Mean age at surgery was 5.47 ± 2.82 (range 1.50–13.2). Eight (47.1%) were female. Preoperative deficit of elevation in adduction was −4 in all children. At the end of surgery, all eyes were freely elevated on adduction, on forced duction test. Mean follow-up time of 26.24 ± 11.22 (range 11–53) months. In 15 of 17 children (88.2%), motility improved, orthotropia in primary position was achieved, and head posture eliminated ( p < 0.001). Superior oblique palsy occurred in two children, who after reoperation, achieved an acceptable outcome. No intraoperative complications were recorded.Conclusion:The superior oblique split tendon elongation procedure is a useful surgical technique with stable and satisfying outcomes for the treatment of severe congenital Brown’s syndrome.

Transcriptomic and genetic analyses identify the Krüppel-like factor dar1 as a master regulator of tube-shaped long tendon development

To ensure locomotion and body stability, the active role of muscle contractions relies on a stereotyped muscle pattern set in place during development. This muscle patterning requires a precise assembly of the muscle fibers with the skeleton via a specialized connective tissue, the tendon. Despite evident disparities, little is known about the molecular basis of tendon diversity. Like in vertebrate limbs, Drosophila leg muscles make connections with specific long tendons that extend through different segments. During leg disc development, cell precursors of long tendons rearrange and collectively migrate to form a tube-shaped structure. A specific developmental program underlies this unique feature of tendon-like cells in the Drosophila model. We provide for the first time a transcriptomic profile of leg tendon precursors through fluorescence-based cell sorting. From promising candidates, we identified the Krüppel-like factor dar1 as a critical actor of leg tendon development. Specifically expressed in leg tendon precursors, loss of dar1 disrupts actin-rich filopodia formation and tendon elongation. Our findings show that dar1 acts downstream of stripe as a critical regulator of cytoskeleton remodeling and mediates the recruitment of new stripe-positive tendon progenitors in a cell non-autonomous manner.

Stretch-Shortening Cycle Performance and Muscle–Tendon Properties in Dancers and Runners

The purpose of this investigation was to elucidate whether ankle joint stretch-shortening cycle performance, isometric and isokinetic plantarflexion strength, and maximal Achilles tendon force and elongation differ between dancers, endurance runners, and untrained controls. To differentiate between dancers, endurance runners, and controls, the authors measured maximal Achilles tendon force and elongation during isometric ramp contractions with ultrasonic imaging, maximal isometric and isokinetic plantarflexion strength with dynamometry, and stretch-shortening cycle function during countermovement hopping and 30-cm drop hopping with a custom-designed sled. The Achilles tendon of dancers elongated significantly (P ≤ .05) more than runners and controls. Dancers were significantly stronger than controls during isometric contractions at different ankle angles. Concentric and eccentric strength during isokinetic contractions at 60°·s−1 and 120°·s−1 was significantly higher in dancers and runners than controls. Dancers hopped significantly higher than runners and controls during hopping tasks. Dancers also possessed significantly greater countermovement hop relative peak power, drop hop relative impulse, and drop hop relative peak power than controls. Finally, dancers reached significantly greater velocities during countermovement hops than runners and controls. Our findings suggest dancing and running require or likely enhance plantarflexion strength. Furthermore, dancing appears to require and enhance ankle joint stretch-shortening cycle performance and tendon elongation.

Changes in Tendon Elongation and Muscle Atrophy Over Time After Achilles Tendon Rupture Repair: A Prospective Cohort Study on the Effects of Early Functional Mobilization

Background: Early functional mobilization (EFM) may improve patient outcome after Achilles tendon rupture (ATR). However, whether EFM affects patient outcome via changes in tendon elongation, thickening, or calf muscle atrophy is unknown. Purpose: To analyze differences in tendon and muscle morphology recovery over time between groups treated with EFM or standard treatment after ATR repair. Study Design: Cohort study; Level of evidence, 2. Methods: This prospective cohort study included 86 patients (20 women) with ATR repair who had a mean (SD) age of 39.3 (8.2) years and were part of a larger prospective randomized controlled trial. Patients were postoperatively randomized to immediate postoperative weightbearing and ankle motion (EFM group) or to immobilization in a below-knee plaster cast for 2 weeks (control group). Patient-reported and functional outcomes were assessed at 6 and 12 months with the Achilles Tendon Total Rupture Score and the heel-rise test for endurance. At 2 and 6 weeks and 6 and 12 months postoperatively, B-mode ultrasound imaging was performed to assess the length and cross-sectional area (CSA) of the Achilles tendon, the gastrocnemius CSA, as well as the thickness of soleus. Results: The Achilles Tendon Total Rupture Score for the EFM and control groups were 65.8 (18.7) and 56.8 (20.1; P = .045), respectively, at 6 months and 79.6 (15.8) and 78.9 (17.2; P = .87), respectively, at 12 months. At 2 weeks, tendon elongation was significantly more pronounced in the EFM group as compared with the control group (mean side-to-side difference, 1.88 cm vs 0.71 cm; P = .005). Subsequently, tendon elongation increased in the control group while it decreased in the EFM group so that at 6 and 12 months no significant differences between groups were found. Mean Achilles tendon elongation at 1 year was 1.73 (1.07) cm for the EFM group (n = 55) and 1.67 (0.92) cm for the control group (n = 27), with a mean difference of 0.06 cm (95% CI, 0.54 to –0.42; P = .80). Achilles tendon CSA and calf muscle atrophy displayed no significant differences between the groups; however, significant changes were demonstrated over time ( P ≤ .001) in both groups. Conclusion: EFM results in more Achilles tendon elongation at early healing, but this difference subsides over time. EFM does not seem to affect patient outcome via changes in tendon elongation, thickening, or calf muscle atrophy. Registration: NCT02318472 (ClinicalTrials.gov identifier).

Tendon elongation with bovine pericardium in strabismus surgery—indications beyond Graves’ orbitopathy

Background For some patients with complex ocular motility disorders, conventional strabismus surgery is insufficient. Surgery with tendon elongation allows correction of larger angles and maintains a sufficient arc of contact for rectus muscles. This study reports results for tendon elongation with bovine pericardium (Tutopatch®) in indications other than Graves’ orbitopathy in which it is already widely used. Methods We reviewed the records of all patients who underwent surgery with Tutopatch® in our institution. Angles of squint and head postures were analyzed preoperatively, on the first postoperative day, and in the long term (median 9 weeks after the operation). Patients with Graves’ orbitopathy were excluded. Results From 2011 to 2018, the procedures on 58 eyes of 54 patients (35 females, median age 35 years (3–75)) met the inclusion criteria. Horizontal rectus muscle surgery (53 eyes) was conducted on patients with residual strabismus (13), Duane’s retraction syndrome with eso- (type I: 16)/exodeviation (type II: 2, type III: 1), 6th (7)/3rd nerve palsy (7), Möbius syndrome (2), congenital fibrosis of the extraocular muscles type 3A (CFEOM3A, TUBB3 mutation) (4), and orbital apex syndrome (1). Vertical rectus muscle surgery (5 eyes) was conducted on patients with myasthenia (1), vertical tropia after orbital floor fracture (1), CFEOM1 (2), and Parry-Romberg syndrome (1). 42 eyes had prior eye muscle surgery (1–5 procedures, median 1). Out of 45 patients with postoperative long-term data, 43 showed an angle reduction. Fifty-one percent had an angle of 10Δ (prism diopter) or less, one had a significant over-effect, and 10 had revision surgery. For the heterogeneous group of residual eso- and exotropias, the median absolute horizontal angle was reduced from 35Δ (16 to 45Δ) to 9Δ (0 to 40Δ), for Duane’s retraction syndrome from 27.5Δ (9 to 40Δ) to 7Δ (0 to 40Δ), and for sixth and third nerve palsies from 43Δ (20 to 75Δ) to 18Δ (4 to 40Δ). For 3 patients with vertical rectus muscle surgery, the median absolute vertical angle was reduced from 30Δ (20 to 45Δ) to 4Δ (1 to 22Δ). The motility range was shifted in the direction contrary to the elongated muscle in all subgroups. A considerable reduction of the excursion into the field of action of the elongated muscle had to be registered. Conclusions Strabismus surgery with bovine pericardium introduces new surgical options for complicated revisions and for rare and complex oculomotor dysfunctions. Yet, it has to be recognized that this type of surgery aiming at maximum effects, despite preservation or restitution of the arc of contact, leads to reduction of the excursion into the field of action of the elongated muscle. Furthermore, dose finding can be difficult depending on the underlying pathology and more than one intervention might be necessary for optimal results.

Relationship Between Recurrent Adductus Deformity of the Forefoot and Achilles Tendon Elongation Following Ponseti Treatment in Children with Idiopathic Clubfoot

Background: Many authors have highlighted the role of muscle strength imbalance around the ankle in the development of recurrent clubfoot following Ponseti treatment. Nevertheless, this possible underlying mechanism behind recurrences has not been investigated sufficiently to date. This study aimed to explore whether there is a relationship between Achilles tendon elongation and recurrent metatarsus adductus deformity in children with unilateral clubfeet treated by Ponseti method. Methods: A retrospective chart review was performed on 20 children (14 boys, 6 girls; mean age: 7 years; age range: 5-9) with a recurrent metatarsus adductus deformity treated by the Ponseti method for unilateral idiopathic clubfoot. At the final follow-up, isometric muscle strength was measured using a portable, hand-held dynamometer in reciprocal muscle groups of the ankle. The length of the tendons around the ankle was ultrasonographically measured. Results: The plantar flexion/dorsiflexion ratio was lower on the involved side (p = 0.001). No significant differences in the strength ratio of inversion/eversion were found (p = 0.4). No difference was observed in lengths of tibialis anterior and posterior tendon (p = 0,1), but Achilles tendon was longer on the involved side (p = 0.001; p &lt; 0.01). A significant negative correlation was discovered between involved/uninvolved Achilles tendon length ratios and involved/uninvolved plantar flexion strength ratios (r = −0.524; p = 0.02) Conclusions: Achilles tendon elongation may be a contributor to the muscle imbalance in clubfeet with the relapsed forefoot adduction treated by the Ponseti technique.