Association of vitamins B1 and B2 intake with early-onset sarcopenia in the general adult population of the US: a cross-sectional study of NHANES data from 2011 to 2018.

Background: Early-onset sarcopenia refers to the progressive loss of muscle mass and function that occurs at an early age. This condition perpetuates the vicious cycle of muscle loss and is associated with adverse outcomes. It is important to identify the contributing factors for early intervention and prevention. While diet is known to impact muscle mass, the association of B vitamins with early-onset sarcopenia remains unexplored. Objectives: To investigate the association of B vitamins intake with early-onset sarcopenia risk in a cross-sectional study. Methods: We conducted data analysis on a total of 8,711 participants aged between 20 and 59 years who took part in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. Early-onset sarcopenia was defined as a SMI measured by DXA that was one standard deviation below the sex-specific mean of the reference population. B vitamins intake (B1, B2, B3, B6, B9, and B12) was assessed by 24-h dietary recall. We used weighted multiple logistic regression and RCS models to estimate the OR and 95% CI of sarcopenia by B vitamins intake, adjusting for demographic, physical, lifestyle, comorbidities, and nutritional covariates. Results: Higher intake of vitamin B1 was associated with a 22% lower sarcopenia risk (OR = 0.78, CI = 0.63-0.97, p = 0.022), and higher intake of vitamin B2 with a 16% lower risk (OR = 0.84, CI = 0.74-0.97, p = 0.012) in both genders. Gender-specific analyses showed a 28% reduction in sarcopenia risk among males with each additional mg of vitamin B1 intake (OR = 0.72, CI = 0.52-0.97, p = 0.038), and a 26% decrease among females with each additional mg of vitamin B2 intake (OR = 0.74, CI = 0.57-0.96, p = 0.021). No significant differences were found between vitamin B2 and males, or between vitamin B1 and females. The RCS model suggested a nonlinear relationship between vitamin B2 intake and sarcopenia risk (POverall = 0.001, PNonlinear = 0.033), with a plateau effect above 3 mg/d. Conclusion: Higher intake of vitamin B1 and B2 may lower the risk of early-onset sarcopenia, with gender differences. This suggests the potential of nutritional intervention by increasing these vitamins intake through diet and supplements. Further research is warranted to elucidate the mechanisms and design targeted interventions.

Haglund resection versus Haglund non-resection for calcific insertional Achilles tendinopathy with Haglund deformity: A retrospective study.

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). CONCLUSION: 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.

A novel and efficient murine model for investigating tendon-to-bone healing.

BACKGROUND: Tendon-to-bone healing is a critical challenge in sports medicine, with its cellular and molecular mechanisms yet to be explored. An efficient murine model could significantly advance our understanding of this process. However, most existing murine animal models face limitations, including a propensity for bleeding, restricted operational space, and a steep learning curve. Thus, the need for a novel and efficient murine animal model to investigate the cellular and molecular mechanisms of tendon-to-bone healing is becoming increasingly evident. METHODS: In our study, forty-four 9-week-old male C57/BL6 mice underwent transection and reattachment of the Achilles tendon insertion to investigate tendon-to-bone healing. At 2 and 4 weeks postoperatively, mice were killed for histological, Micro-CT, biomechanical, and real-time polymerase chain reaction tests. RESULTS: Histological staining revealed that the original tissue structure was disrupted and replaced by a fibrovascular scar. Although glycosaminoglycan deposition was present in the cartilage area, the native structure had been destroyed. Biomechanical tests showed that the failure force constituted approximately 44.2% and 77.5% of that in intact tissues, and the ultimate tensile strength increased from 2 to 4 weeks postoperatively. Micro-CT imaging demonstrated a gradual healing process in the bone tunnel from 2 to 4 weeks postoperatively. The expression levels of ACAN, SOX9, Collagen I, and MMPs were detected, with all genes being overexpressed compared to the control group and maintaining high levels at 2 and 4 weeks postoperatively. CONCLUSIONS: Our results demonstrate that the healing process in our model is aligned with the natural healing process, suggesting the potential for creating a new, efficient, and reproducible mouse animal model to investigate the cellular and molecular mechanisms of tendon-to-bone healing.

Exercise-induced Musclin determines the fate of fibro-adipogenic progenitors to control muscle homeostasis.

The effects of exercise on fibro-adipogenic progenitors (FAPs) are unclear, and the direct molecular link is still unknown. In this study, we reveal that exercise reduces the frequency of FAPs and attenuates collagen deposition and adipose formation in injured or disused muscles through Musclin. Mechanistically, Musclin inhibits FAP proliferation and promotes apoptosis in FAPs by upregulating FILIP1L. Chromatin immunoprecipitation (ChIP)-qPCR confirms that FoxO3a is the transcription factor of FILIP1L. In addition, the Musclin/FILIP1L pathway facilitates the phagocytosis of apoptotic FAPs by macrophages through downregulating the expression of CD47. Genetic ablation of FILIP1L in FAPs abolishes the effects of exercise or Musclin on FAPs and the benefits on the reduction of fibrosis and fatty infiltration. Overall, exercise forms a microenvironment of myokines in muscle and prevents the abnormal accumulation of FAPs in a Musclin/FILIP1L-dependent manner. The administration of exogenous Musclin exerts a therapeutic effect, demonstrating a potential therapeutic approach for muscle atrophy or acute muscle injury.

Inhibition of IKKß via a DNA-Based In Situ Delivery System Improves Achilles Tendinopathy Healing in a Rat Model.

BACKGROUND: The inhibition of IKKß by the inhibitor 2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-(4-piperidinyl)-3-pyridine carbonitrile (ACHP) is a promising strategy for the treatment of Achilles tendinopathy. However, the poor water solubility of ACHP severely hinders its in vivo application. Moreover, the effective local delivery of ACHP to the tendon and its therapeutic effects have not been reported. PURPOSE: To investigate the therapeutic effects of IKKß inhibition via injection of ACHP incorporated into a DNA supramolecular hydrogel in a collagenase-induced tendinopathy rat model. STUDY DESIGN: Controlled laboratory study. METHODS: Dendritic DNA, a Y-shaped monomer, and a crosslinking monomer were mixed with ACHP and self-assembled into an ACHP-DNA supramolecular hydrogel (ACHP-Gel). The effects of ACHP-Gel in tendon stem/progenitor cells were investigated via RNA sequencing and validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). A total of 120 collagenase-induced rats were randomly assigned to 5 groups: blank, phosphate-buffered saline (PBS), DNA-Gel, ACHP, and ACHP-Gel. Healing outcomes were evaluated using biomechanic and histologic evaluations at 4 and 8 weeks. RESULTS: ACHP-Gel enhanced the solubility of ACHP and sustained its release for ≥21 days in vivo, which significantly increased the retention time of ACHP and markedly reduced the frequency of administration. RNA sequencing and qRT-PCR showed that ACHP effectively downregulated genes related to inflammation and extracellular matrix remodeling and upregulated genes related to tenogenic differentiation. The cross-sectional area (P = .024), load to failure (P = .002), stiffness (P = .039), and elastic modulus (P = .048) significantly differed between the ACHP-Gel and PBS groups at 8 weeks. The ACHP-Gel group had better histologic scores than the ACHP group at 4 (P = .042) and 8 weeks (P = .009). Type I collagen expression (COL-I; P = .034) and the COL-I/collagen type III ratio (P = .015) increased while interleukin 6 expression decreased (P < .001) in the ACHP-Gel group compared with the ACHP group at 8 weeks. CONCLUSION: DNA supramolecular hydrogel significantly enhanced the aqueous solubility of ACHP and increased its release-retention time. Injection frequency was markedly reduced. ACHP-Gel suppressed inflammation in Achilles tendinopathy and promoted tendon healing in a rat model. CLINICAL RELEVANCE: ACHP-Gel injection is a promising strategy for the treatment of Achilles tendinopathy in clinical practice.

PPP1R3A inhibits osteogenesis and negatively regulates intracellular calcium levels in calcific tendinopathy.

Calcific tendinopathy (CT) is defined by the progressive accumulation of calcium crystals in tendonic regions that results in severe pain in patients. The etiology of CT is not fully elucidated. In this study, we elucidate the role of PPP1R3A in CT. A significant decrease in PPP1R3A expression was observed in CT patient tissues, which was further confirmed in tissues from a CT-induced rat model. Overexpression of PPP1R3A ex vivo reduced the expression of osteo/chondrogenic markers OCN and Sox9, improved tendon tissue architecture, and reduced intracellular Ca2+ levels. Overexpression of SERCA2 and knockdown of Piezo1 decreased expression of osteo/chondrogenic markers and intracellular calcium in PPP1R3A-knockdown tendon cells. Lastly, PPP1R3A expression was regulated at the posttranscriptional level by binding of HuR. Collectively, the present study indicates that PPP1R3A plays an important role in regulating calcium homeostasis in tendon cells via Piezo1/SERCA2, rendering it a promising target for therapeutic interventions of CT.

Biomechanical Comparison between Rotational Scarf Osteotomy and Translational Scarf Osteotomy: A Finite Element Analysis.

OBJECTIVE: Rotational Scarf osteotomy has its unique advantages in treating hallux valgus, but it also has certain drawbacks. The biomechanical differences between rotational Scarf and translational Scarf osteotomy are not clear evaluates the correction ability and biomechanical difference of two surgical methods for hallux valgus by finite element analysis. METHODS: The computerized tomography data of a hallux valgus patient were selected to establish a finite element model. The standard Scarf osteotomy was simulated based on the model, and the rotation and translation were performed, respectively. The size of the intermetatarsal angle, contact area, distal metatarsal articular angle and the absolute length of the first metatarsal was compared between the two groups. We completed the cartilage, ligament and other tissues on the bone model to establish a full foot model. We analyzed the troughing, plantar aponeurosis tension, plantar soft tissue, and ground stress and also observed the stability of the fracture site by a three-point bending test. RESULTS: Both surgical methods may effectively correct the intermetatarsal angle. After rotational osteotomy, the contact area increased, and the length of the first metatarsal bone initially increased and then decreased compared to that in the translational group. Furthermore, rotational Scarf significantly increased the distal metatarsal articular angle. Mechanical analysis showed that the cancellous bone in the contact part of the fracture site in the translation group had greater stress, which was the reason for the occurrence of the troughing. Stress distribution of plantar aponeurosis, plantar soft tissue, and the ground showed no significant difference. The three-point bending test showed that the separation of the broken ends of the rotational Scarf osteotomy model (0.133 mm) was slightly smaller than the translational group (0.147 mm). CONCLUSION: Both surgical methods can successfully correct intermetatarsal angle (IMA). Compared to traditional translational Scarf osteotomy, rotational Scarf osteotomy is more conducive to postoperative stability and healing, but it also has certain drawbacks. In clinical practice, individualized surgical methods still need to be selected for different types of patients with hallux valgus.

Supraspinatus Tendon Reconstruction Using Fascia Lata Autograft for Irreparable Posterosuperior Massive Rotator Cuff Tears.

Superior capsule reconstruction has shown good long-term clinical efficacy in treating irreparable posterosuperior massive rotator cuff tears. However, conventional superior capsule reconstruction did not treat the medial supraspinatus tendons. Therefore, dynamic function of the posterosuperior rotator cuff does not restore effectively, especially the function of active abduction and external rotation. We describe a supraspinatus tendon reconstruction technique that presents a stepwise approach to accomplish the dual goals of stable anatomic reconstruction and restoring the dynamic function of the supraspinatus tendon.

Integrative single-cell RNA and ATAC sequencing reveals that the FOXO1-PRDX2-TNF axis regulates tendinopathy.

Introduction: Tendinopathy, the most common form of chronic tendon disorder, leads to persistent tendon pain and loss of function. Profiling the heterogeneous cellular composition in the tendon microenvironment helps to elucidate rational molecular mechanisms of tendinopathy. Methods and results: In this study, through a multi-modal analysis, a single-cell RNA- and ATAC-seq integrated tendinopathy landscape was generated for the first time. We found that a specific cell subpopulation with low PRDX2 expression exhibited a higher level of inflammation, lower proliferation and migration ability, which not only promoted tendon injury but also led to microenvironment deterioration. Mechanistically, a motif enrichment analysis of chromatin accessibility showed that FOXO1 was an upstream regulator of PRDX2 transcription, and we confirmed that functional blockade of FOXO1 activity induced PRDX2 silencing. The TNF signaling pathway was significantly activated in the PRDX2-low group, and TNF inhibition effectively restored diseased cell degradation. Discussion: We revealed an essential role of diseased cells in tendinopathy and proposed the FOXO1-PRDX2-TNF axis is a potential regulatory mechanism for the treatment of tendinopathy.

Effect of treadmill training on fibrocartilage complex repair in tendon-bone insertion healing in the postinflammatory stage.

Aims: Mechanical stimulation is a key factor in the development and healing of tendon-bone insertion. Treadmill training is an important rehabilitation treatment. This study aims to investigate the benefits of treadmill training initiated on postoperative day 7 for tendon-bone insertion healing. Methods: A tendon-bone insertion injury healing model was established in 92 C57BL/6 male mice. All mice were divided into control and training groups by random digital table method. The control group mice had full free activity in the cage, and the training group mice started the treadmill training on postoperative day 7. The quality of tendon-bone insertion healing was evaluated by histology, immunohistochemistry, reverse transcription quantitative polymerase chain reaction, Western blotting, micro-CT, micro-MRI, open field tests, and CatWalk gait and biomechanical assessments. Results: Our results showed a significantly higher tendon-bone insertion histomorphological score in the training group, and the messenger RNA and protein expression levels of type II collagen (COL2A1), SOX9, and type X collagen (COL10A1) were significantly elevated. Additionally, tendon-bone insertion resulted in less scar hyperplasia after treadmill training, the bone mineral density (BMD) and bone volume/tissue volume (BV/TV) were significantly improved, and the force required to induce failure became stronger in the training group. Functionally, the motor ability, limb stride length, and stride frequency of mice with tendon-bone insertion injuries were significantly improved in the training group compared with the control group. Conclusion: Treadmill training initiated on postoperative day 7 is beneficial to tendon-bone insertion healing, promoting biomechanical strength and motor function. Our findings are expected to guide clinical rehabilitation training programmes.

Dynamic Superior Capsular Reconstruction for Irreparable Massive Rotator Cuff Tears: Histologic Analysis in a Rat Model and Short-term Clinical Evaluation.

BACKGROUND: Superior capsular reconstruction (SCR) has been demonstrated to be a valuable treatment for patients with irreparable massive rotator cuff tears (IMRCTs). However, the torn medial supraspinatus (SSP) tendons, which acted as dynamic stabilizers, were left untreated in conventional SCR, and the dynamic force from the SSP tendon was not restored. PURPOSE: To evaluate the effect of dynamic SCR (dSCR) on fascia-to-bone healing in a rat model, and to compare the short-term clinical effectiveness of dSCR and SCR using autologous fascia lata (FL) in patients with IMRCTs. STUDY DESIGN: Controlled laboratory study and cohort study; Level of evidence, 3. METHODS: A total of 50 rats were divided randomly into 2 groups: the dSCR group and the SCR group (25 rats per group). First, chronic IMRCTs were created, and then the torn tendons in both groups were subjected to SCR using autologous thoracolumbar fascial (TLF) grafts. The remnant of the SSP tendon was sutured to the medial part of the TLF graft in the dSCR group but not in the SCR group. Histologic sections were assessed at 1, 2, 4, 8, and 16 weeks postoperatively. In the clinical study, 22 patients (9 SCR, 13 dSCR) were analyzed. The recovery of shoulder function, including the active range of motion (ROM), visual analog scale (VAS), American Shoulder and Elbow Surgeons score, Constant score, and University of California Los Angeles score, acromiohumeral distance (AHD), and fatty infiltration, was evaluated before surgery and at the last follow-up. RESULTS: Histologic analysis of the fascia-to-bone junction in the rat model showed that the TLF gradually migrated into tendon-like tissue over the rotator cuff defects in both groups, and the modified tendon maturation score of the fascia-to-bone interface in the dSCR group was higher than that in the SCR group at 4 weeks (12.20 ± 1.30 vs 14.60 ± 1.52; P = .004), 8 weeks (19.60 ± 1.14 vs 22.20 ± 1.10; P = .019), and 16 weeks (23.80 ± 0.84 vs 26.20 ± 0.84 P = .024). The dSCR group showed earlier fibrocartilage cell formation and angiogenesis. In the clinical study, all 22 patients completed a minimum of 12 months of follow-up after surgery, and the mean follow-up duration was 22.89 ± 7.59 months in the SCR group and 25.62 ± 7.32 months in the dSCR group. The patients in both groups showed significant improvements in terms of ROM, shoulder function scores, and AHD. At the last follow-up, abduction (56.67°± 27.39° vs 86.54°± 30.37°; P = .029), external rotation (25.00°± 9.35° vs 33.08°± 8.55°; P = .049), internal rotation cone rank (-2.78 ± 2.44 vs -4.38 ± 1.12; P = .049), VAS (-3.00 ± 0.87 vs -3.92 ± 0.95; P = .031) and Constant (47.89 ± 15.39 vs 59.15 ± 9.74; P = .048) scores, and the AHD improvement degree (3.06 ± 1.41 mm vs 4.38 ± 1.35 mm; P = .039) in the dSCR group were significantly improved compared with those in the SCR group. The results of fatty infiltration at the last follow-up showed that there was significant improvement compared with the preoperative results in both the conventional SCR (P = .036) and the dSCR (P = .001) groups. However, there were no significant differences between the 2 groups (P = .511). CONCLUSION: dSCR can promote faster fascia-to-bone healing in a rat model, and the dSCR technique could provide a preferable treatment option for patients with IMRCTs. CLINICAL RELEVANCE: dSCR might restore the dynamic of SSP in some sense and then improve the fatty infiltration in the SSP.

Double-bundle reconstruction of the anterior talofibular ligament by partial peroneal brevis tendon.

BACKGROUND: Anatomic anterior talofibular ligament (ATFL) reconstruction with autologous single-bundle tendon has been widely used in the treatment of ATFL injury. However, there are few clinical reports of using the peroneus brevis tendon (PBT) for double-bundle ATFL reconstruction. The aim of this study was to investigate the clinical effect of double-bundle ATFL reconstruction with PBT. METHODS: This was a retrospective review of all patients diagnosed with ATFL injury presenting from August 2019 to December 2021. Fifty-three patients were selected after screening based on the inclusion and exclusion criteria. The following data were compared before and after surgery: Visual Analogue Scale (VAS) score, American Orthopedic Foot and Ankle Society (AOFAS) score, Karlsson Ankle Functional Score (KAFS), the pain interference (PI) and physical function (PF) scores of the Patient-Reported Outcomes Measurement Information System (PROMIS), the diameter and width of PBT in ultrasound and muscle strength. RESULTS: All functional scores (VAS, PI/PF, AO-FAS, KAFS) and muscle strength were significantly improved at the last follow-up (P < 0.05). The diameter and width of the PBT on ultrasound postoperation were smaller than those preoperatively. CONCLUSION: Double-bundle ATFL reconstruction with the partial PBT technique is a feasible, anatomic reconstruction technique for chronic lateral instability of the ankle, which meets the anatomical characteristics of the double bundle of the ligament, and the absence of partial PBT does not affect the peroneal muscle strength. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Copper modified cobalt-chromium particles for attenuating wear particle induced-inflammation and osteoclastogenesis.

The nature of aseptic prosthetic loosening mainly relates to the wear particles that induce inflammation and subsequent osteoclastogenesis. The ideal approach to impede wear particle-induced osteolysis should minimize inflammation and osteoclastogenesis. In this work, Co29Cr9W3Cu particles were used as a research model for the first time to explore the response of Co29Cr9W3Cu particles to inflammatory response and osteoclast activation in vitro and in vivo by using Co29Cr9W particles as the control group. In vitro studies showed that the Co29Cr9W3Cu particles could promote the generation of M2-phenotype macrophages and increase the expression level of anti-inflammatory factor IL-10, while inhibiting the formation of M1-phenotype macrophages and down-regulating the expression of inflammatory factors TNF-α, IL-6 and IL-1ß; More importantly, the Co29Cr9W3Cu particles reduced the expression of NF-κB and downstream osteoclast related-specific transcription marker genes, such as TRAP, NFATc1, and Cath-K; In vivo results indicated that the Co29Cr9W3Cu particles exposed to murine calvarial contributed to decreasing the amount of osteoclast and osteolysis area. These findings collectively demonstrated that Cu-bearing cobalt-chromium alloy may potentially delay the development of aseptic prosthetic loosening induced by wear particles, which is expected to provide evidence of Co29Cr9W3Cu alloy as an alternative material of joint implants with anti-wear associated osteolysis.

Comparison of cortical versus cancellous bone fixation in tendon-to-bone healing with a rat trans-calcaneal suture model for Achilles tendon sleeve avulsion.

BACKGROUND: Trans-calcaneal suture technique is an economical and effective method for repairing Achilles tendon sleeve avulsion. Whether cancellous bone fixation upon this technique could accelerate tendon-to-bone healing is unknown. The purpose of this study is to compare the effect of cortical versus cancellous bone fixation on tendon-bone healing with a novel rat trans-calcaneal suture model. METHODS: Trans-calcaneal suture treatment was carried out on the right hindlimb in male Sprague-Dawley rats (N = 80). They were randomly divided into the cortical group (Achilles fixed to the calcaneal cortical bone, n = 40) and the cancellous group (Achilles fixed to the calcaneal cancellous bone, n = 40). Gait analysis and immunohistochemistry were performed 1, 4, 7, and 14 days after the operation. Gross observation, biomechanical analysis, micro-CT, and histological analysis were performed 4 and 8 weeks after surgery. Independent-samples t tests were used for comparison between groups. RESULTS: At 1, 4, and 7 days, the swing time of the affected limb in the cancellous group decreased, while the duty cycle, the maximum contact area, the print area, and the mean intensity increased significantly. The cross-sectional area of the tendon-bone junction in the cancellous group was smaller, and the failure load and stiffness were higher 4 weeks after the operation. The cancellous group showed more proportion of new bone and a relatively well-organized and dense connective tissue interface with better fibrocartilage-like tissue at 4 weeks after the operation. The ratio of ED2 + macrophages in the cancellous group was significantly higher than in the cortical group on 1, 4, 7, and 14 days. There were no significant differences in gait at 2 weeks, in appearance, biomechanics, new bone formation, and histology at 8 weeks after surgery between the two groups. CONCLUSION: In the new rat trans-calcaneal suture model, cancellous fixation can accelerate tendon-to-bone healing in the early stage, which perhaps is related to the abundant bone marrow tissue in the cancellous bone that modulates the inflammatory processes.

Comparison of Suture Button and Syndesmotic Screw for Ankle Syndesmotic Injuries: A Meta-analysis of Randomized Controlled Trials.

Background: The syndesmotic screw (SS) and suture button (SB) fixation methods are both widely used for the reduction of ankle syndesmotic injury, with varying outcomes. Purpose: To review recently published randomized controlled trials (RCTs) to assess the outcomes between SS and SB fixation for ankle syndesmotic injury. Study Design: Systematic review; Level of evidence, 1. Methods: The PubMed, Embase, ClinicalTrials.gov, and Cochrane databases were searched for relevant RCTs published between 1966 and 2021 according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Eligible studies were RCTs comparing SS and SB fixation for ankle syndesmotic injury. The risk of bias was evaluated using the Cochrane Risk of Bias tool. Primary outcomes included complications, malreduction, and unplanned reoperation, and secondary outcomes were the American Orthopaedic Foot & Ankle Society (AOFAS) score, Olerud-Molander ankle score (OMAS), and EuroQol-5 Domain (EQ-5D) score. The mean difference (MD) and risk ratio (RR) were calculated for continuous and dichotomous outcomes, respectively. Random- or fixed-effects model was applied according to heterogeneity. Results: Of 389 studies, 8 RCTs involving 512 patients were included. Overall, 257 patients received SS fixation and 255 patients received SB fixation. The 2 groups did not differ significantly in malreduction (RR, -0.06; 95% CI, -0.18 to 0.07) or EQ-5D (MD, 0.01; 95% CI, -0.01 to 0.03). However, the SB group showed significant advantages over the SS group in complications (RR, 0.42; 95% CI, 0.26 to 0.66), unplanned reoperation (RR, 0.62; 95% CI, 0.43 to 0.89), AOFAS score (MD, 3.04; 95% CI, 1.77 to 4.31), and OMAS (MD, 4.51; 95% CI, 1.54 to 7.48). The risk of bias of the included studies was acceptable. Conclusion: The results showed that there were no significant differences between the SS and SB groups in malreduction and EQ-5D scores. However, the SB group had significantly better local irritation rates, unplanned reoperation rates, AOFAS scores, and OMASs.

Micropattern Silk Fibroin Film Facilitates Tendon Repair In Vivo and Promotes Tenogenic Differentiation of Tendon Stem/Progenitor Cells through the α2ß1/FAK/PI3K/AKT Signaling Pathway In Vitro.

Background: Tendon injuries are common clinical disorders. Due to the limited regeneration ability of tendons, tissue engineering technology is often used as an adjuvant treatment. This study explored the molecular pathways underlying micropattern SF film-regulated TSPC propensity and their repairing effects to highlight the application value of micropattern SF films. Methods: First, we characterized the physical properties of the micropattern SF films and explored their repairing effects on the injured tendons in vivo. Then, we seeded TSPCs on SF films in vitro and determined the micropattern SF film-induced gene expression and activation of signaling pathways in TSPCs through high-throughput RNA sequencing and proteomics assays. Results: The results of in vivo studies suggested that micropattern SF films can promote remodeling of the injured tendon. In addition, immunohistochemistry (IHC) results showed that tendon marker genes were significantly increased in the micropattern SF film repair group. Transcriptomic and proteomic analyses demonstrated that micropattern SF film-induced genes and proteins in TSPCs were mainly enriched in the focal adhesion kinase (FAK)/actin and phosphoinositide 3-kinase (PI3K)/AKT pathways. Western blot analysis showed that the expression of integrins α2ß1, tenascin-C (TNC), and tenomodulin (TNMD) and the phosphorylation of AKT were significantly increased in the micropattern SF film group, which could be abrogated by applying PI3K/AKT inhibitors. Conclusion: Micropattern SF films modified by water annealing can promote remodeling of the injured tendon in vivo and regulate the tendon differentiation of TSPCs through the α2ß1/FAK/PI3K/AKT signaling pathway in vitro. Therefore, they have great medical value in tendon repair.

N-Acetyl-L-cysteine facilitates tendon repair and promotes the tenogenic differentiation of tendon stem/progenitor cells by enhancing the integrin α5/ß1/PI3K/AKT signaling.

BACKGROUND: Tendon injury is associated with oxidative stress, leading to reactive oxygen species (ROS) production and inflammation. N-acetyl-L-cysteine (NAC) is a potent antioxidant. However, how NAC affects the biological functions of tendon stem/progenitor cells (TSPCs) and tendon repair has not been clarified.  METHOD: The impacts of NAC on the viability, ROS production, and differentiation of TSPCs were determined with the cell counting kit-8, fluorescence staining, Western blotting, and immunofluorescence. The effect of NAC on gene transcription in TSPCs was analyzed by transcriptomes and bioinformatics and validated by Western blotting. The potential therapeutic effect of NAC on tendon repair was tested in a rat model of Achilles tendon injury. RESULTS: Compared with the untreated control, treatment with 500 µM NAC greatly promoted the proliferation of TSPCs and significantly mitigated hydrogen peroxide-induced ROS production and cytotoxicity in vitro. NAC treatment significantly increased the relative protein expression of collagen type 1 alpha 1 (COL1A1), tenascin C (TNC), scleraxis (SCX), and tenomodulin (TNMD) in TPSCs. Bioinformatics analyses revealed that NAC modulated transcriptomes, particularly in the integrin-related phosphoinositide 3-kinase (PI3K)/AKT signaling, and Western blotting revealed that NAC enhanced integrin α5ß1 expression and PI3K/AKT activation in TSPCs. Finally, NAC treatment mitigated the tendon injury, but enhanced the protein expression of SCX, TNC, TNMD, and COLIA1 in the injured tissue regions of the rats. CONCLUSION: NAC treatment promoted the survival and differentiation of TSPCs to facilitate tendon repair after tendon injury in rats. Thus, NAC may be valuable for the treatment of tendon injury.

Inhibition of CX3CL1 by treadmill training prevents osteoclast-induced fibrocartilage complex resorption during TBI healing.

Introduction: The healing of tendon-bone injuries is very difficult, often resulting in poor biomechanical performance and unsatisfactory functional recovery. The tendon-bone insertion has a complex four distinct layers structure, and previous studies have often focused on promoting the regeneration of the fibrocartilage layer, neglecting the role of its bone end repair in tendon-bone healing. This study focuses on the role of treadmill training in promoting bone regeneration at the tendon-bone insertion and its related mechanisms. Methods: After establishing the tendon-bone insertion injury model, the effect of treadmill training on tendon-bone healing was verified by Micro CT and HE staining; then the effect of CX3CL1 on osteoclast differentiation was verified by TRAP staining and cell culture; and finally the functional recovery of the mice was verified by biomechanical testing and behavioral test. Results: Treadmill training suppresses the secretion of CX3CL1 and inhibits the differentiation of local osteoclasts after tendon-bone injury, ultimately reducing osteolysis and promoting tendon bone healing. Discussion: Our research has found the interaction between treadmill training and the CX3CL1-C3CR1 axis, providing a certain theoretical basis for rehabilitation training.

Single-cell analysis reveals that Jinwu Gutong capsule attenuates the inflammatory activity of synovial cells in osteoarthritis by inhibiting AKR1C3.

Jinwu Gutong capsule (JGC) is a traditional Chinese medicine formula for the treatment of osteoarthritis (OA). Synovitis is a typical pathological change in OA and promotes disease progression. Elucidating the therapeutic mechanism of JGC is crucial for the precise treatment of OA synovitis. In this study, we demonstrate that JGC effectively inhibits hyperproliferation, attenuates inflammation, and promotes apoptosis of synovial cells. Through scRNA-seq data analysis of OA synovitis, we dissected two distinct cell fates that influence disease progression (one fate led to recovery while the other fate resulted in deterioration), which illustrates the principles of fate determination. By intersecting JGC targets with synovitis hub genes and then mimicking picomolar affinity interactions between bioactive compounds and binding pockets, we found that the quercetin-AKR1C3 pair exhibited the best affinity, indicating that this pair constitutes the most promising molecular mechanism. In vitro experiments confirmed that the expression of AKR1C3 in synovial cells was reduced after JGC addition. Further overexpression of AKR1C3 significantly attenuated the therapeutic efficacy of JGC. Thus, we revealed that JGC effectively treats OA synovitis by inhibiting AKR1C3 expression.