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Bone regeneration and repair are crucial to ambulation and quality of life. Factors such as poor general health, serious medical comorbidities, chronic inflammation, and ageing can lead to delayed healing and nonunion of fractures, and persistent bone defects. Bioengineering strategies to heal bone often involve grafting of autologous bone marrow aspirate concentrate (BMAC) or mesenchymal stem cells (MSCs) with biocompatible scaffolds. While BMAC shows promise, variability in its efficacy exists due to discrepancies in MSC concentration and robustness, and immune cell composition. Understanding the mechanisms by which macrophages and lymphocytes – the main cellular components in BMAC – interact with MSCs could suggest novel strategies to enhance bone healing. Macrophages are polarized into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, and influence cell metabolism and tissue regeneration via the secretion of cytokines and other factors. T cells, especially helper T1 (Th1) and Th17, promote inflammation and osteoclastogenesis, whereas Th2 and regulatory T (Treg) cells have anti-inflammatory pro-reconstructive effects, thereby supporting osteogenesis. Crosstalk among macrophages, T cells, and MSCs affects the bone microenvironment and regulates the local immune response. Manipulating the proportion and interactions of these cells presents an opportunity to alter the local regenerative capacity of bone, which potentially could enhance clinical outcomes. Cite this article: Bone Joint Res 2024;13(9):462–473.

Advanced glycation end-products (AGEs) play a critical supportive role during musculoskeletal disorders via glycosylation and oxidative stress. Though apocynin, identified as a potent and selective inhibitor of NADPH oxidase, has been reported to be involved in pathogen-induced reactive oxygen species (ROS), its role in age-related rotator cuff degeneration has not been well clarified. Therefore, this study aims to evaluate the in vitro effects of apocynin on human rotator cuff-derived cells. Twelve patients with rotator cuff tears (RCTs) participated in the study. Supraspinatus tendons from patients with RCTs were collected and cultured. After the preparation of RC-derived cells, they were divided into four groups (control group, control + apocynin group, AGEs group, AGEs + apocynin group), and gene marker expression, cell viability, and intracellular ROS production were evaluated. The gene expression of NOX, IL-6, and the receptor for AGEs (RAGE) was significantly decreased by apocynin. We also examined the effect of apocynin in vitro. The results showed that ROS induction and increasing apoptotic cells after treatment of AGEs were significantly decreased, and cell viability increased considerably. These results suggest that apocynin can effectively reduce AGE-induced oxidative stress by inhibiting NOX activation. Thus, apocynin is a potential prodrug in preventing degenerative changes of the rotor cuff.

Carpal tunnel syndrome (CTS) is caused by subsynovial connective tissue fibrosis, resulting in median nerve (MN) mobility. The standard evaluation method is the measurement of the MN cross-sectional area using static images, and dynamic images are not widely used. In recent years, remarkable progress has been made in the field of deep learning (DL) in medical image processing. The aim of the present study was to evaluate MN dynamics in CTS hands using the YOLOv5 model, which is one of the object detection models of DL. We included 20 normal hands (control group) and 20 CTS hands (CTS group). We obtained ultrasonographic short-axis images of the carpal tunnel and the MN and recorded MN motion during finger flexion–extension, and evaluated MN displacement and velocity. The YOLOv5 model showed a score of 0.953 for precision and 0.956 for recall. The radial–ulnar displacement of the MN was 3.56 mm in the control group and 2.04 mm in the CTS group, and the velocity of the MN was 4.22 mm/s in the control group and 3.14 mm/s in the CTS group. The scores were significantly reduced in the CTS group. This study demonstrates the potential of DL-based dynamic MN analysis as a powerful diagnostic tool for CTS.

Abstract Background Quercetin, a flavonoid abundantly in vegetables and fruits, exerts antioxidant and anti-inflammatory effects. We investigated the protective effects of quercetin against oxidative stress in the Achilles tendons of diabetic rats. Methods Cells were collected from the Achilles tendons of Sprague–Dawley rats and cultured under four conditions: regular glucose (RG) without quercetin (Quer-), RG with quercetin (Quer +), high-glucose (HG) Quer-, and HG Quer + . The expression of genes related to NADPH oxidase (NOX) and inflammation, reactive oxygen species accumulation, and apoptosis rates was analyzed. Additionally, diabetic rats were divided into two groups and subjected to quercetin (group Q) or no quercetin (group C) treatment. Histological evaluation and expression analysis of relevant genes in the Achilles tendon were performed. Results In rat tendon-derived cells, the expression of Nox1, Nox4, and Il6; reactive oxygen species accumulation; and apoptosis rates were significantly decreased by quercetin treatment in the HG group. The collagen fiber arrangement was significantly disorganized in the diabetic rat Achilles tendons in group C compared with that in group Q. The mRNA and protein expression levels of NOX1 and NOX4 were significantly decreased upon quercetin treatment. Furthermore, the expression of Il6, type III collagen, Mmp2, and Timp2 was significantly decreased, whereas that of type I collagen was significantly increased in group Q compared with that in group C. Conclusions Quercetin treatment decreases NOX expression and thus exerts antioxidant and anti-inflammatory effects in the Achilles tendons of diabetic rats. Quercetin treatment may be effective against diabetic tendinopathy.

Abstract Background Most degenerative rotator cuff tears (RCTs) are associated with a limited range of motion (ROM) of the shoulder joint. Additionally, patients with diabetes mellitus (DM) show a higher frequency of limited ROM. Recently, advanced glycation end products (AGEs) of proteins have been observed to cause tissue fibrosis, primarily through abnormal collagen cross-linking and oxidative stress. In this study, we investigated the effect of AGEs on ROM limitation in the shoulder capsule and its relationship with DM in the patients with RCTs. Methods Sixteen patients (eight in the DM and non-DM groups) who underwent arthroscopic surgery for RCT with limited shoulder ROM were included in this study. AGE-related pathologies in both groups were compared, and the relationship between AGE accumulation and shoulder joint ROM was evaluated. Shoulder capsule tissue was harvested and subjected to histological and in vitro evaluation. Results The DM group displayed high levels of AGEs and reactive oxygen species (ROS), and reduced cell viability. There was a significant positive correlation between ROS expression, apoptosis, and preoperative hemoglobin A1c. ROS expression, apoptosis, and ROM of the shoulder joint showed a negative correlation. The NADPH oxidase (NOX) expression and collagen III/I ratio were significantly higher in the DM group than in the non-DM group. Conclusions The DM group showed significant AGEs deposition in the shoulder capsule. Additionally, there was a significant association between AGEs and ROM limitation. Collectively, the findings suggest that the oxidative stress induced by AGEs deposition, which leads to fibrosis and local inflammation, might contribute to the limited ROM of the shoulder joint in patients with RCTs accompanied by DM.

Local cell therapy has recently gained attention for the treatment of joint diseases and fractures. Mesenchymal stem cells (MSCs) are not only involved in osteogenesis and angiogenesis, but they also have immunomodulatory functions, such as inducing macrophage migration during bone regeneration via macrophage crosstalk. C-C motif chemokine ligand 2 (CCL2), a known inflammatory mediator, is associated with the migration of macrophages during inflammation. This study examined the utility of CCL2 as a therapeutic target for local cell therapy. Using lentiviral vectors for rabbit MSCs, genetically modified CCL2 overexpressing MSCs were generated. Osteogenic differentiation assays were performed using MSCs with or without macrophages in co-culture, and cell migration assays were also performed. Additionally, co-cultures were performed with endothelial cells (ECs), and angiogenesis was evaluated using a tube formation assay. Overexpression of CCL2 did not affect bone formation under monoculture conditions but promoted chemotaxis and osteogenesis when co-cultured with macrophages. Furthermore, CCL2-overexpression promoted tube formation in co-culture with ECs. These results suggest that CCL2 induces macrophage chemotaxis and osteogenesis by promoting crosstalk between MSCs and macrophages; CCL2 also stimulates ECs to induce angiogenesis. These findings indicate that CCL2 may be a useful therapeutic target for local cell therapy in areas of bone loss.

There are no reports investigating the relationship between shoulder range of motion (ROM) and pitching elbow torque in junior high school pitchers. Therefore, we aimed to evaluate the factors associated with medial elbow torque in this population. Sixty-three junior high school baseball pitchers were recruited for this study. The participants completed a questionnaire and passive ROM measurements of shoulder abduction and horizontal adduction. All pitchers pitched three fastballs at maximum effort while wearing a wireless sensor recording pitching mechanics and elbow valgus torque for each pitch. Age (r = 0.65, p < 0.001), height (r = 0.83, p < 0.001), body weight (r = 0.82, p < 0.001), BMI (r = 0.60, p < 0.001), and ball velocity (r = 0.80, p < 0.001) were significantly positively correlated with elbow valgus torque. Participants were divided into two groups based on elbow valgus torque, >30 (high torque [HT]) and

Abstract Tendon rupture and nerve injury cause fatty infiltration of the skeletal muscle, and the adipokines secreted from the infiltrated adipocytes are known to contribute to chronic inflammation. Therefore, in this study, we evaluated the effects of the adipokines on chronic inflammation using a rat sciatic nerve-crushed injury model. In vitro and in vivo experiments showed that the expression of adiponectin was decreased (0.3-fold) and the expression of Il6 (~ 3.8-fold) and Tnf (~ 6.2-fold) was increased in the nerve-crushed group compared to that in the control group. It was also observed that the administration of an adiponectin receptor agonist decreased the levels of Il6 (0.38-fold) and Tnf (0.28-fold) and improved cellular viability (~ 1.9-fold) in vitro. Additionally, in the fatty infiltrated skeletal muscle, low adiponectin levels were found to be associated with chronic inflammation. Therefore, the local administration of adiponectin receptor agonists would prevent chronic inflammation.

Substantial advancements in markerless motion capture accuracy exist, but discrepancies persist when measuring joint angles compared to those taken with a goniometer. This study integrates machine learning techniques with markerless motion capture, with an aim to enhance this accuracy. Two artificial intelligence-based libraries—MediaPipe and LightGBM—were employed in executing markerless motion capture and shoulder abduction angle estimation. The motion of ten healthy volunteers was captured using smartphone cameras with right shoulder abduction angles ranging from 10° to 160°. The cameras were set diagonally at 45°, 30°, 15°, 0°, −15°, or −30° relative to the participant situated at a distance of 3 m. To estimate the abduction angle, machine learning models were developed considering the angle data from the goniometer as the ground truth. The model performance was evaluated using the coefficient of determination R2 and mean absolute percentage error, which were 0.988 and 1.539%, respectively, for the trained model. This approach could estimate the shoulder abduction angle, even if the camera was positioned diagonally with respect to the object. Thus, the proposed models can be utilized for the real-time estimation of shoulder motion during rehabilitation or sports motion.

Abstract Background The accurate assessment of distal radioulnar joint (DRUJ) instability is still challenging as there is no established objective evaluation method. This study aimed to develop a noninvasive measurement method using a three-dimensional electromagnetic sensor system (EMS) to quantitatively assess and characterize the normal DRUJ movement in healthy volunteers. Methods The DRUJ movement was mimicked using both a block model and saw bone. Movement of the models was measured by EMS, and the accuracy and reproducibility of the measurements were assessed. In vivo measurement was performed in a sitting position with the elbow flexed and the forearm pronated. One sensor each was attached to the distal radial shaft and the ulnar head. The examiners fixed the distal radius and the carpal bones, moved the ulnar head from the dorsal to the volar side and measured the dorsovolar translation. The volar translation was measured by EMS and ultrasonography, and the correlation coefficient was calculated. The dorsovolar translation was evaluated in 14 healthy volunteers (7 men and 7 women) by three hand surgeons. The intraclass and inter-rater correlation coefficients (ICCs), the differences between the dominant and non-dominant sides and between men and women were assessed. Results The accuracy and reproducibility assessment results of the EMS showed high accuracy and reproducibility. In the comparison between EMS and ultrasonography, the correlation coefficient was 0.920 (p = 0.16 × 10-3). The ICC (1,5) for the intra-rater reliability was 0.856, and the ICC (2,5) for inter-rater reliability was 0.868. The mean ulnar head translation and difference between dominant and non-dominant sides were 6.00 ± 1.16 mm (mean ± SD) and − 0.12 ± 0.40 mm, respectively. There were no significant differences between any of the parameters. Conclusions A new measurement method using EMS could evaluate DRUJ movement with high accuracy, reproducibility, and intra- and inter-rater reliability. In healthy volunteers, the dorsovolar ulnar head translation was 6.00 mm. The difference between the dominant and non-dominant sides was < 1.0 mm with no significant difference. EMS provided an objective, non-invasive, real-time assessment of dynamic changes in the DRUJ. These findings could be useful in the treatment of patients with DRUJ instability.

The coracohumeral ligament (CHL) is related to the range of motion of the shoulder joint. The evaluation of the CHL using ultrasonography (US) has been reported on the elastic modulus and thickness of the CHL, but no dynamic evaluation method has been established. We aimed to quantify the movement of the CHL by applying Particle Image Velocimetry (PIV), a technique used in the field of fluid engineering, to cases of shoulder contracture using the US. The subjects were eight patients, with 16 shoulders. The coracoid process was identified from the body surface, and a long-axis US image of the CHL parallel to the subscapularis tendon was drawn. The shoulder joint was moved from 0 degrees of internal/external rotation to 60 degrees of internal rotation at a rhythm of one reciprocation every 2 s. The velocity of the CHL movement was quantified by the PIV method. The mean magnitude velocity of CHL was significantly faster on the healthy side. The maximum magnitude velocity was significantly faster on the healthy side. The results suggest that the PIV method is helpful as a dynamic evaluation method, and in patients with shoulder contracture, the CHL velocity was significantly decreased.

The diagnosis of osteoporosis is made by measuring bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA). Machine learning, one of the artificial intelligence methods, was used to predict low BMD without using DXA in elderly women. Medical records from 2541 females who visited the osteoporosis clinic were used in this study. As hyperparameters for machine learning, patient age, body mass index (BMI), and blood test data were used. As machine learning models, logistic regression, decision tree, random forest, gradient boosting trees, and lightGBM were used. Each model was trained to classify and predict low-BMD patients. The model performance was compared using a confusion matrix. The accuracy of each trained model was 0.772 in logistic regression, 0.739 in the decision tree, 0.775 in the random forest, 0.800 in gradient boosting, and 0.834 in lightGBM. The area under the curve (AUC) was 0.595 in the decision tree, 0.673 in logistic regression, 0.699 in the random forest, 0.840 in gradient boosting, and 0.961, which was the highest, in the lightGBM model. Important features were BMI, age, and the number of platelets. Shapley additive explanation scores in the lightGBM model showed that BMI, age, and ALT were ranked as important features. Among several machine learning models, the lightGBM model showed the best performance in the present research.

The subsheath of the extensor carpi ulnaris (ECU) tendon, a component of the triangular fibrocartilage complex (TFCC), is particularly important as it dynamically stabilizes the distal radioulnar joint. However, the relationship between TFCC injury and ECU dynamics remains unclear. This study aimed to analyze ECU movement and morphology using ultrasonography (US) images. Twenty wrists of patients with TFCC injury, who underwent TFCC repair, were included in the injury group, and 20 wrists of healthy volunteers were in the control group. For static image analysis, curvature and linearity ratios of the ECU in US long-axis images captured during radioulnar deviation were analyzed. For dynamic analysis of the ECU, the wrist was moved from radial deviation to ulnar deviation at a constant speed, and the velocity of the tendon was analyzed using particle image velocimetry. The static analysis showed that the ECU tendon was more curved in ulnar deviation in the injury group than in the control group, and the dynamic analysis showed that only vertical velocity toward the deep side during ulnar deviation was higher in the injury group. These results suggest that TFCC injury caused ECU curvature during ulnar deviation and increased the vertical velocity of the ECU during wrist deviation.

Most shoulder rotator cuff tears (RCTs) are caused by non-traumatic age-related rotator cuff degeneration, of which hyperglycemia is a risk factor due to its glycation reaction and oxidative stress. We aimed to identify the influence of diabetes-induced glycation and oxidative stress in patients with non-traumatic shoulder RCTs. Twenty patients, aged over 50 years, with non-traumatic shoulder RCTs participated in this study. Patients with a history of diabetes mellitus or preoperative HbA1c ≥ 6.5% were assigned to the diabetic group (n = 10), and the rest to the non-diabetic group (n = 10). Cell proliferation; expression of genes related to oxidative stress, glycation reaction, inflammation, and collagen; intracellular reactive oxygen species (ROS) levels; and apoptosis rates were analyzed. The diabetic group had significantly lower cell proliferation than the non-diabetic group. In the diabetic group, the mRNA expression levels of NOX1, NOX4, IL6, RAGE, type III collagen, MMP2, TIMP1, and TIMP2 were significantly higher; type I collagen expression was significantly lower; and the rate of ROS-positive cells and apoptotic cells, as well as the expression of advanced glycation end-products (AGEs) and the receptor for AGEs (RAGE), was significantly higher. In conclusion, hyperglycemia caused by diabetes mellitus increased AGE and RAGE expression, and led to increased NOX expression, ROS production, and apoptosis in the human rotator cuff. This provides scope to find a preventive treatment for non-traumatic RCTs by inhibiting glycation and oxidative stress.

Although electromyography is the routine diagnostic method for cubital tunnel syndrome (CuTS), imaging diagnosis by measuring cross-sectional area (CSA) with ultrasonography (US) has also been attempted in recent years. In this study, deep learning (DL), an artificial intelligence (AI) method, was used on US images, and its diagnostic performance for detecting CuTS was investigated. Elbow images of 30 healthy volunteers and 30 patients diagnosed with CuTS were used. Three thousand US images were prepared per each group to visualize the short axis of the ulnar nerve. Transfer learning was performed on 5000 randomly selected training images using three pre-trained models, and the remaining images were used for testing. The model was evaluated by analyzing a confusion matrix and the area under the receiver operating characteristic curve. Occlusion sensitivity and locally interpretable model-agnostic explanations were used to visualize the features deemed important by the AI. The highest score had an accuracy of 0.90, a precision of 0.86, a recall of 1.00, and an F-measure of 0.92. Visualization results show that the DL models focused on the epineurium of the ulnar nerve and the surrounding soft tissue. The proposed technique enables the accurate prediction of CuTS without the need to measure CSA.

The triangular fibrocartilage complex (TFCC) is a significant stabilizer of the distal radioulnar joint. Diagnosing TFCC injury is currently difficult, but ultrasonography (US) has emerged as a low-cost, minimally invasive diagnostic tool. We aimed to quantitatively analyze TFCC by performing motion analysis by using US. Twelve healthy volunteers, comprising 24 wrists (control group), and 15 patients with TFCC Palmer type 1B injuries (injury group) participated. The US transducer was positioned between the ulnar styloid process and triquetrum and was tilted ulnarly 30° from the vertical line. The wrist was then actively moved from 10° of radial deviation to 20° of ulnar deviation in a 60-rounds-per-minute rhythm that was paced by a metronome. The articular disc displacement velocity magnitude was analyzed by using particle image velocimetry fluid measurement software. The mean area of the articular discs was larger on ulnar deviation in the control group. The mean articular disc area on radial deviation was larger in the injury group. The average articular disc velocity magnitude for the injury group was significantly higher than that for the control group. The results suggest that patients with TFCC injury lose articular disc cushioning and static stability, and subsequent abnormal motion can be analyzed by using US.

The moment arm of gluteus medius proportionated to distance from femoral head tends to be decreased postoperatively in valgus-impacted femoral neck fractures treated by in situ internal fixation. The aim of this article is to introduce a new gentle technique to correct the deformity. The innovative technique of Minimally Invasive Closed Reduction for Impacted Femoral neck fractures (MICRIF) mainly focused to disimpact valgus neck fractures into anatomical position. Patients were positioned on the fracture table to fix the hip joint in abduction and internal rotation. A 2.4-mm diameter Kirschner wire was inserted a few centimetres outside the iliac crest piercing the acetabular beak to enter the femoral head, followed by repositioning of the lower extremity from abduction into neutral. This method provides satisfactory anatomical reduction. Thereafter, a surgical implant was applied to osteosynthesize the reduced fracture. This simple technique effectively provides anatomical reduction in valgus impacted femoral neck fracture.

Background: In patients with femoral intertrochanteric fractures treated by cephalomedullary (CM) nailing, abduction force reportedly decreased by 25–30% during the postoperative follow-up period. The purpose of the current study is to evaluate the cross-sectional area (CSA) and adipose tissue ratio (ATR) of the gluteus medius muscle on the postoperative computed tomography (CT) view, expecting this graphic study will support clinical results. Materials and methods: A total of 27 patients with femoral intertrochanteric fractures treated by CM femoral nail implants completed the study. The mean age at osteosynthesis was 83 years (range: 72–94 years). The mean postoperative follow-up period was 23 months. The three CT axial slice views were defined as slices A, B, and C corresponding to proximal, midway, and distal part of gluteus medius, respectively. The CSA and ATR were assessed bilaterally. Results: The mean and standard deviation of CSA values (mm 2 ) between the nonoperated/ operated side were as follows: slice A: 2225.8 ± 621.2/1984.5 ± 425.8; slice B: 2145.1 ± 538.3/1854.9 ± 383.9; and slice C: 1711.0 ± 459.0/1434.5 ± 396.9 ( p < 0.01 in slices A, B, and C). The mean and standard deviation of ATR values (%) from the nonoperative/ operative side were as follows: slice A: 2.8 ± 1.7/5.2 ± 3.5; slice B: 2.7 ± 1.9/4.6 ± 3.2; and slice C: 3.6 ± 3.0/4.8 ± 3.2 ( p < 0.01 in slices A and B and p < 0.05 in slice C). Conclusion: Our image findings documented that gluteus medius is significantly changed in CSA and ATR. The damage possibly triggers decrease in muscular strength of hip abduction in the postoperative follow-up period. This measurement is objective, and needed no patient’s endurance and cooperation.

Mallet fingers with an avulsion fracture of the distal phalanx or rupture of the terminal tendon of the extensor mechanism is known as a common injury, while mallet thumb is very rare. In this paper, the case of a 19-year-old woman with a sprained left thumb sustained while playing basketball is presented. Plain radiographs and computed tomography revealed an avulsion fracture involving more than half of the articular surface at the base of the distal phalanx. Closed reduction and percutaneous fixation were performed using the two extension block Kirschner wires’ technique under digital block anesthesia. At 4 months postoperatively, the patient had achieved excellent results according to Crawford’s evaluation criteria and had no difficulties in working or playing basketball. Various conservative and operative treatment strategies have been reported for management of mallet thumb. We chose the two extension block Kirschner wires’ technique to minimize invasion of the extensor mechanism and nail bed and to stabilize the large fracture fragment.