Dickkopf-1 (DKK1) blockade mitigates osteogenesis imperfecta (OI) related bone disease.

BACKGROUND: The current treatment of osteogenesis imperfecta (OI) is imperfect. Our study thus delves into the potential of using Dickkopf-1 antisense (DKK1-AS) to treat OI. METHODS: We analysed serum DKK1 levels and their correlation with lumbar spine and hip T-scores in OI patients. Comparative analyses were conducted involving bone marrow stromal cells (BMSCs) and bone tissues from wild-type mice, untreated OI mice, and OI mice treated with DKK1-ASor DKK1-sense (DKK1-S). RESULTS: Significant inverse correlations were noted between serum DKK1 levels and lumbar spine (correlation coefficient = - 0.679, p = 0.043) as well as hip T-scores (correlation coefficient = - 0.689, p = 0.042) in OI patients. DKK1-AS improved bone mineral density (p = 0.002), trabecular bone volume/total volume fraction (p < 0.001), trabecular separation (p = 0.010), trabecular thickness (p = 0.001), trabecular number (p < 0.001), and cortical thickness (p < 0.001) in OI mice. DKK1-AS enhanced the transcription of collagen 1α1, osteocalcin, runx2, and osterix in BMSC from OI mice (all p < 0.001), resulting in a higher von Kossa-stained matrix area (p < 0.001) in ex vivo osteogenesis assays. DKK1-AS also reduced osteoclast numbers (p < 0.001), increased ß-catenin and T-cell factor 4 immunostaining reactivity (both p < 0.001), enhanced mineral apposition rate and bone formation rate per bone surface (both p < 0.001), and decreased osteoclast area (p < 0.001) in OI mice. DKK1-AS upregulated osteoprotegerin and downregulated nuclear factor-kappa B ligand transcription (both p < 0.001). Bone tissues from OI mice treated with DKK1-AS exhibited significantly higher breaking force compared to untreated OI mice (p < 0.001). CONCLUSIONS: Our study elucidates that DKK1-AS has the capability to enhance bone mechanical properties, restore the transcription of osteogenic genes, promote osteogenesis, and inhibit osteoclastogenesis in OI mice.

Pathological, Morphometric and Correlation Analysis of the Modified Mankin Score, Tidemark Roughness and Calcified Cartilage Thickness in Rat Knee Osteoarthritis after Extracorporeal Shockwave Therapy.

The paper displayed the pathological changes and relationships of the modified Mankin score, tidemark roughness and calcified cartilage (CC) thickness by extracorporeal shockwave therapy (ESWT) (0.25 mJ/ mm2 with 800 impulses) on different positions of the medial and lateral rat knee OA joint. After the experiments, the articular cartilage was assessed using histomorphometry, image analysis and statistical method. In the micro-CT analysis, ESWT on medial groups were better than lateral groups in the trabecular volume and trabecular number. The data showed a strong negative correlation between the modified Mankin score and tidemark roughness (r = -0.941; P < 0.001). In terms of the relationship of tidemark roughness with CC thickness, the medial and Sham groups showed a significant negative correlation (r = -0.788, P = 0.022). Additionally, the Euclidean distance derived from 3D scatter plot analysis was an indicator of chondropathic conditions, exhibiting a strong correlation with OA stage in the articular cartilage of the femur (r = 0.911, P < 0.001) and tibia (r = 0.890, P < 0.001) after ESWT. Principle component analysis (PCA) further demonstrated that ESWT applied to medial locations had a better outcome than treatment at lateral locations for knee OA by comparing with Sham and OA groups, and CC thickness was the most important factor affecting hyaline cartilage repair after ESWT.

Clinical and radiologic outcomes of the modified phemister procedure with coracoclavicular ligament augmentation using mersilene tape versus hook plate fixation for acute acromioclavicular joint dislocation.

BACKGROUND: The clinical superiority of surgical treatment for acromioclavicular (AC) joint dislocation remains controversial. The aim of this study was to compare the clinical and radiological outcomes of the modified Phemister procedure with CC ligament augmentation using Mersilene tape to those of hook plate fixation for acute AC joint dislocation. METHODS: In this study, patients who received modified Phemister surgery with CC ligament augmentation using Mersilene tape (PM group) or hook plate fixation (HK group) for acute unstable AC joint dislocation with a minimum 5-year follow-up period were retrospectively reviewed. The clinical outcomes were evaluated according to blood loss during surgery, surgical duration, visual analogue scale (VAS), Constant-Murley score (CMS), University of California at Los Angeles (UCLA) shoulder rating scale, and the occurrence of complications. Radiological outcomes were assessed from radiographs according to multiple parameters, including CC distance maintenance, acromion osteolysis, and the presence of distal clavicle osteolysis. RESULTS: A total of 35 patients completed follow-up for more than 5 years and were analyzed in this study (mean = 74.08 months). There were 18 patients in the PM group and 17 in the HK group. The PM group exhibited similar improvement in functional outcome to the HK group. Regarding radiological outcomes, the HK group had a superior performance in terms of CC distance maintenance, of statistical significance (CCDR: 94.29 ± 7.01% versus 111.00 ± 7.69%, p < 0.001) after a one-year follow-up period. However, there were 4 cases of acromion osteolysis and 2 cases of distal clavicle osteolysis in the HK group. CONCLUSION: Hook plate fixation was found to be superior to the modified Phemister technique with CC ligament augmentation using Mersilene tape in terms of CC distance maintenance, but there was no significant difference in the functional outcome after 5 years of follow-up. Both surgical methods are reliable options for the treatment of acute AC joint dislocation. Modified Phemister surgery with CC ligament augmentation using Mersilene tape is a relatively lower-cost option for acute AC joint dislocation without the need of a second surgery for implant removal.

Outcome and Predictors of Septic Failure Following Total Joint Arthroplasty for Prior Septic Arthritis of Hip and Knee Joint.

BACKGROUND: Arthroplasty patients with prior septic arthritis are at a high risk of developing periprosthetic joint infection (PJI). The aims of this study are to investigate the outcome and predictors of septic failure following total joint arthroplasty (TJA) for prior septic arthritis. In addition, the optimal timing of TJA is also discussed. METHODS: A retrospective review of 105 TJA patients with prior septic arthritis between January 2000 and December 2019 was performed. Patient-specific and surgery-related factors, organism profiles, and other relevant variables were recorded. RESULTS: At a mean follow-up of 10.3 years, the PJI rate was 16.2%. The adjusted Cox proportional hazards model showed that male gender (HR, 9.95; P < .01), end-stage renal disease (HR, 37.34; P < .01), debridement surgery ≥3 times (HR,4.75; P = .04) and polymicrobial infection in primary septic arthritis (HR, 10.02; P = .02) were independent risk factors for PJI. Neither the types of initial debridement, nor one-stage vs two-stage arthroplasty was related to the risk of PJI. While delaying the timing of TJA did not correlate with a reduction of PJI rate, there was a higher risk of PJI re-infection by the same microorganisms isolated in prior septic arthritis if TJA was performed within 6 months after septic arthritis. CONCLUSIONS: Our study demonstrated that male gender, end-stage renal disease (ESRD), multiple debridement surgeries and polymicrobial septic arthritis predisposed septic failure of TJA following prior septic arthritis. Surgeons should counsel patients with the potential complications, and be cognizant about the risk factors pertaining to septic failure when considering TJA.

Is coracoclavicular reconstruction necessary in hook plate fixation for acute unstable acromioclavicular dislocation?

BACKGROUND: Acromioclavicular joint (ACJ) dislocation is a relatively common shoulder injury. For the treatment of cases of severe ACJ dislocation (Rockwood type III-V), hook plate fixation is an easy-to-master and minimally-invasive approach to surgical intervention. Over stress on the acromion following hook plate fixation often leads to acromial complications such as osteolysis and loss of reduction. We hypothesized that suspensory reconstruction alongside hook plate fixation might provide a superior stability and reduce complications as compared with hook plate fixation alone. The purpose of the study was to assess the clinical and radiographic outcomes of these two surgical modalities. METHODS: We retrospectively enrolled 49 patients with acute ACJ dislocation from May 2010 to December 2018. Among them, 19 patients received hook plate fixation only (HP group), and 19 underwent concomitant hook plate fixation and loop suspension fixation with two mersilene sutures (HM group). The demographic data of the patients were recorded and analyzed. All patients underwent a shoulder X-ray initially, immediately postoperatively, and at 1, 3, 6 and 12 months to measure the relative coracoclavicular distance (rCCD). Clinical assessment of shoulder function outcome was conducted using the Constant Murley Score (CMS); the University of California at Los Angeles (UCLA) Shoulder Score was also measured at the latest follow-up. RESULTS: There were no significant differences in the demographic data between the two groups. With regards to the CMS and the UCLA score, the HM group and HP group both had excellent outcomes, and no significant differences in scores were observed between groups (CMS: 93.90 ± 6.16 versus 94.47 ± 7.26, p = 0.47; UCLA score: 32.84 ± 2.91 versus 34.32 ± 1.16, p = 0.07). However, the HM group demonstrated substantial superiority in terms of maintenance of the rCCD over the HP group (91.47 ± 27.47 versus 100.75 ± 48.70, p = 0.015). In addition, there was less subacromial osteolysis in the HM group than the HP group (52.6% versus 15.8%, p = 0.038). CONCLUSION: Both fixations yielded excellent functional outcomes. However, concomitant hook plate fixation with loop suspensory reconstruction demonstrated the fewer acromion complications and statistical differences in reduction maintenance with less clinical significance.

MicroRNA-29a in Osteoblasts Represses High-Fat Diet-Mediated Osteoporosis and Body Adiposis through Targeting Leptin.

Skeletal tissue involves systemic adipose tissue metabolism and energy expenditure. MicroRNA signaling controls high-fat diet (HFD)-induced bone and fat homeostasis dysregulation remains uncertain. This study revealed that transgenic overexpression of miR-29a under control of osteocalcin promoter in osteoblasts (miR-29aTg) attenuated HFD-mediated body overweight, hyperglycemia, and hypercholesterolemia. HFD-fed miR-29aTg mice showed less bone mass loss, fatty marrow, and visceral fat mass together with increased subscapular brown fat mass than HFD-fed wild-type mice. HFD-induced O2 underconsumption, respiratory quotient repression, and heat underproduction were attenuated in miR-29aTg mice. In vitro, miR-29a overexpression repressed transcriptomic landscapes of the adipocytokine signaling pathway, fatty acid metabolism, and lipid transport, etc., of bone marrow mesenchymal progenitor cells. Forced miR-29a expression promoted osteogenic differentiation but inhibited adipocyte formation. miR-29a signaling promoted brown/beige adipocyte markers Ucp-1, Pgc-1α, P2rx5, and Pat2 expression and inhibited white adipocyte markers Tcf21 and Hoxc9 expression. The microRNA also reduced peroxisome formation and leptin expression during adipocyte formation and downregulated HFD-induced leptin expression in bone tissue. Taken together, miR-29a controlled leptin signaling and brown/beige adipocyte formation of osteogenic progenitor cells to preserve bone anabolism, which reversed HFD-induced energy underutilization and visceral fat overproduction. This study sheds light on a new molecular mechanism by which bone integrity counteracts HFD-induced whole-body fat overproduction.

Piezoelectric Microvibration Mitigates Estrogen Loss-Induced Osteoporosis and Promotes Piezo1, MicroRNA-29a, and Wnt3a Signaling in Osteoblasts.

Biophysical stimulation alters bone-forming cell activity, bone formation and remodeling. The effect of piezoelectric microvibration stimulation (PMVS) intervention on osteoporosis development remains uncertain. We investigated whether 60 Hz, 120 Hz, and 180 Hz PMVS (0.05 g, 20 min/stimulation, 3 stimulations/week for 4 consecutive weeks) intervention affected bone integrity in ovariectomized (OVX) mice or osteoblastic activity. PMVS (120 Hz)-treated OVX mice developed fewer osteoporosis conditions, including bone mineral density loss and trabecular microstructure deterioration together with decreased serum resorption marker CTX-1 levels, as compared to control OVX animals. The biomechanical strength of skeletal tissue was improved upon 120 Hz PMVS intervention. This intervention compromised OVX-induced sparse trabecular bone morphology, osteoblast loss, osteoclast overburden, and osteoclast-promoting cytokine RANKL immunostaining and reversed osteoclast inhibitor OPG immunoreactivity. Osteoblasts in OVX mice upon PMVS intervention showed strong Wnt3a immunoreaction and weak Wnt inhibitor Dkk1 immunostaining. In vitro, PMVS reversed OVX-induced loss in von Kossa-stained mineralized nodule formation, Runx2, and osteocalcin expression in primary bone-marrow stromal cells. PMVS also promoted mechanoreceptor Piezo1 expression together with increased microRNA-29a and Wnt3a expression, whereas Dkk1 rather than SOST expression was repressed in MC3T3-E1 osteoblasts. Taken together, PMVS intervention promoted Piezo1, miR-29a, and Wnt signaling to upregulate osteogenic activity and repressed osteoclastic bone resorption, delaying estrogen deficiency-induced loss in bone mass and microstructure. This study highlights a new biophysical remedy for osteoporosis.

Sural nerve sensory response in diabetic distal symmetrical polyneuropathy.

INTRODUCTION: The sural sensory nerve action potential (SNAP) amplitude is a measure of the number of axons. We tested the hypothesis that sural SNAP amplitude can be used as a marker in screening, severity evaluation, and follow-up of diabetic distal symmetrical polyneuropathy (DSPN). METHODS: Patients with type 2 diabetes underwent nerve conduction studies and were followed for 6 years. Composite amplitude scores (CASs) were determined to evaluate DSPN severity. RESULTS: Sural SNAP amplitudes were negatively correlated with CAS (r = -.790, P < .0001), and changes in sural SNAP amplitudes were negatively correlated with those of CAS after controlling for follow-up duration (r = -.531, P = .028). DISCUSSION: When a patient's baseline sural SNAP amplitude is above zero, it can be used as one measure of DSPN in screening, severity evaluation, and follow-up. However, if the patient's sural SNAP value is zero, CAS can be used as a follow-up measure.

Use of Antimicrobial-Impregnated Incise Drapes to Prevent Periprosthetic Joint Infection in Primary Total Joint Arthroplasty: A Retrospective Analysis of 9774 Cases.

BACKGROUND: Antimicrobial-impregnated incise drapes are often used despite any literature that demonstrates a reduction in the rate of periprosthetic joint infection (PJI). The aim of this study is to compare the efficacy of antimicrobial-impregnated incise drapes with nonantimicrobial-impregnated incise drapes for the prevention of PJI in patients undergoing total joint arthroplasty (TJA). METHODS: A retrospective study of 9774 primary TJAs from 2000 to 2012 was performed. Patients who received an antimicrobial-impregnated incise drape (n = 5241) were compared with patients who received a nonantimicrobial-impregnated incise drape (n = 4533). The decision to use an antimicrobial drape was based on the surgeon's discretion. Patients who developed PJI within 1 year after index surgery were identified. Multivariate logistic regression analysis and sensitivity analysis using propensity score matching were performed to control for potential confounders. RESULTS: The overall PJI rate was 1.14% (60 of 5241) for patients who received an antimicrobial-impregnated incise drape compared with 1.26% (57 of 4533) for those with a nonantimicrobial-impregnated incise drape. There was no difference in the PJI rate between patients with an antimicrobial-impregnated incise drape and those who received nonantimicrobial-impregnated incise drape in the univariate (odds ratio [OR] = 0.91; 95% confidence interval [CI] = 0.63-1.30), multivariate (adjusted OR = 0.92; 95% CI, 0.63-1.34), or propensity score matching analysis (OR = 0.84; 95% CI = 0.52-1.35). CONCLUSION: Despite the increasing adoption of the use of antimicrobial-impregnated incise drapes in our institute, this study suggests that antimicrobial-impregnated incise drapes do not reduce PJI in patients undergoing primary TJAs.

Systemic effects of platelet-rich plasma local injection on serum and urinary anabolic metabolites: A prospective randomized study.

Platelet-rich plasma (PRP) is widely utilized in the treatment of sports injuries. However, potential systemic effects after localized PRP injection are unclear at present. In this prospective randomized study, 24 Taiwanese male athletes with tendinopathy were randomized into a PRP group (n = 13) or a saline group (n = 11). The concentrations of serum and urine biomarkers were quantified by enzyme-linked immunosorbent assay assessment as well as gas chromatographic and mass spectrometric analysis, respectively. The results showed no significant differences in serum levels of growth hormone, insulin-like growth factor-1, insulin-like growth factor-binding protein 3, vascular endothelial growth factor, platelet-derived growth factor-BB, or serum substance P(SP) between the two groups before intervention, nor at 1, 2, or 7 days after intervention. However, a significant decrease in the serum SP level 1 and 7 days after PRP injection was observed. Regarding urinary concentrations of metabolites of anabolic androgenic steroids (AAS), no between-group differences before intervention, nor at 1, 2, or 7 days after intervention, were observed. Our study failed to observe significant surge of serum anabolic molecules and urinary excretion of anabolic AAS metabolites after PRP injection.

Shockwave Therapy Combined with Autologous Adipose-Derived Mesenchymal Stem Cells Is Better than with Human Umbilical Cord Wharton's Jelly-Derived Mesenchymal Stem Cells on Knee Osteoarthritis.

Extracorporeal shockwave therapy (ESWT) and mesenchymal stem cells (MSCs) have been reported to have chondroprotective effects in knee osteoarthritis (OA). Here, we examined whether autologous adipose-derived mesenchymal stem cells (ADMSCs) and human umbilical cord Wharton's jelly-derived mesenchymal stem cells (WJMSCs) increased the efficacy of ESWT in knee OA, and compared the efficacy of the two. The treatment groups exhibited significant improvement of knee OA according to pathological analysis, micro-computed tomography (CT), and immunohistochemistry (IHC) staining. The ADMSCs and ESWT+ADMSCs groups exhibited increased trabecular thickness and bone volume as compared with the ESWT, WJMSCs, and ESWT+WJMSCs groups individually. According to the results of IHC staining, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) activity and caspase-3 were significantly reduced in the ADMSCs and ESWT+ADMSCs groups as compared with the WJMSCs and ESWT+WJMSC groups. In mechanistic factor analysis, the synergistic effect of ESWT+ADMSCs was observed as being greater than the efficacies of other treatments in terms of expressions of transforming growth factor (TGF)-ß, runt-related transcription factor (RUNX)-2 and sex determining region Y-box (SOX)-9. The type II collagen was expressed at a higher level in the WJMSCs group than in the others. Furthermore, ESWT+ADMSCs reduced the expression of platelet-derived growth factor (PDGF)-BB and increased the expression of bone morphogenetic protein (BMP)-4. Therefore, we demonstrated that ESWT+ADMSCs had a synergistic effect greater than that of ESWT+WJMSCs for the treatment of early knee OA.

Effects of computer-assisted navigation versus the conventional technique for total knee arthroplasty on levels of plasma thrombotic markers: a prospective study.

BACKGROUND: Venous thromboembolism (VTE) is a major sequela after total knee arthroplasty (TKA). We prospectively compared the differences in the perioperative plasma D-dimer and fibrinogen levels between the individuals undergoing TKA via computer-assisted navigation and via a conventional method as the surrogate comparison for VTE. There were 174 patients fulfilling the inclusion criteria and providing valid informed consent between September 2011 and November 2013. There were 69 females and 20 males in the navigation-assisted group (median age: 71.00 years), while the conventional group was composed of 59 females and 26 males (median age: 69.00 years). Blood samples were obtained prior to and at 24 and 72 h after surgery for measurement of the levels of plasma D-dimer and fibrinogen. RESULTS: A significantly lower plasma D-dimer level 24 h after TKA (p = 0.001) and a milder postoperative surge 24 h after TKA (p = 0.002) were observed in patients undergoing navigation-assisted TKA. The proportions of subjects exceeding the plasma D-dimer cut-off values of 7.5, 8.6 and 10 mg/L 24 h after TKA were all significantly higher in the conventional group than in the navigation-assisted group (p = 0.024, 0.004, and 0.004, respectively). CONCLUSIONS: A lower plasma D-dimer level and a milder surge in the plasma D-dimer level were observed in patients undergoing navigation-assisted TKA in comparison with patients undergoing conventional TKA 24 h after surgery. These findings may supplement the known advantages of navigation-assisted TKA.

Inferior outcome of rotator cuff repair in chronic hemodialytic patients.

BACKGROUND: Repair of rotator cuff tears has yielded excellent functional outcomes in recent decades; however, poor outcomes and dissatisfaction have been noted in specific groups. Spontaneous tendon rupture has been reported in patients receiving long-term hemodialysis owing to alteration of tendon structure, which might impede functional recovery after rotator cuff repair. The purpose of the present study was to compare the clinical outcomes between hemodialysis and non-hemodialysis patients after rotator cuff repair. METHODS: We retrospectively reviewed patients who underwent mini-open rotator cuff repair from Jan 2013 to Jan 2017. A total of 14 patients under chronic hemodialysis (HD) were matched to non-hemodialysis (NHD) patients at a 1:2 ratio according to age, gender, tear size, severity of fatty infiltration and history of diabetes. Pre- and post-operative functional outcome was assessed using the simple shoulder test (SST), American Shoulder and Elbow Surgeons (ASES), Shoulder Rating Scale of the University of California at Los Angeles (UCLA) and visual analog scale (VAS) scores. Clinical functional outcome at the last follow-up was adopted for comparison of the HD and NHD groups. RESULTS: A total of 42 patients were enrolled in this comparative study, with a mean age of 66.64 ± 1.68 years in the HD group and 65.71 ± 5.40 years in the NHD group. At the final clinical assessment, the post-operative functional outcome was significantly improved in both groups (p < 0.001). However, the functional outcome of the HD group was significantly inferior to that of the NHD group in terms of the SST score (6.50 ± 2.24 vs 9.39 ± 1.87, p < 0.001), ASES score (63.17 ± 15.93 vs 86.96 ± 11.43, p < 0.001), UCLA score (20.14 ± 7.71 vs 29.82 ± 5.08, p < 0.001) and VAS score (3.00 ± 0.96 vs 1.21 ± 1.03, p < 0.001). CONCLUSION: The improvement of pain and functional improvement of long-term hemodialysis patients were inferior to those of patients without hemodialysis after mini-open rotator cuff repair.

Low-Energy Extracorporeal Shock Wave Ameliorates Streptozotocin Induced Diabetes and Promotes Pancreatic Beta Cells Regeneration in a Rat Model.

Traditional therapy for diabetes mellitus has focused on supportive treatment, and is not significant in the promotion of pancreatic beta cells regeneration. We investigated the effect of low- energy extracorporeal shock wave (SW) on a streptozotocin induced diabetes (DM) rat model. METHODS: The DM rats were treated with ten sessions of low-energy SW therapy (weekly for ten consecutive weeks) or left untreated. We assessed blood glucose, hemoglobin A1c (HbA1c), urine volume, pancreatic islets area, c-peptide, glucagon-like peptide 1 (GLP-1) and insulin production, beta cells number, pancreatic tissue inflammation, oxidative stress, apoptosis, angiogenesis, and stromal cell derived factor 1 (SDF-1) ten weeks after the completion of treatment. RESULTS: The ten- week low-energy SW therapy regimen significantly reduced blood glucose, HbA1c, and urine volume as well as significantly enhancing pancreatic islets area, c-peptide, GLP-1, and insulin production in the rat model of DM. Moreover, low-energy SW therapy increased the beta cells number in DM rats. This was likely primarily attributed to the fact that low-energy SW therapy reduced pancreatic tissue inflammation, apoptosis, and oxidative stress as well as increasing angiogenesis, cell proliferation, and tissue repair potency. CONCLUSIONS: Low-energy SW therapy preserved pancreatic islets function in streptozotocin-induced DM. Low-energy SW therapy may serve as a novel noninvasive and effective treatment of DM.

MicroRNA-29a Mitigates Subacromial Bursa Fibrosis in Rotator Cuff Lesion with Shoulder Stiffness.

Rotator cuff lesion with shoulder stiffness is a major cause of shoulder pain and motionlessness. Subacromial bursa fibrosis is a prominent pathological feature of the shoulder disorder. MicroRNA-29a (miR-29a) regulates fibrosis in various tissues; however, the miR-29a action to subacromial bursa fibrosis remains elusive. Here, we reveal that subacromial synovium in patients with rotator cuff tear with shoulder stiffness showed severe fibrosis, hypertrophy, and hyperangiogenesis histopathology along with significant increases in fibrotic matrices collagen (COL) 1A1, 3A1, and 4A1 and inflammatory cytokines, whereas miR-29a expression was downregulated. Supraspinatus and infraspinatus tenotomy-injured shoulders in transgenic mice overexpressing miR-29a showed mild swelling, vascularization, fibrosis, and regular gait profiles as compared to severe rotator cuff damage in wild-type mice. Treatment with miR-29a precursor compromised COL3A1 production and hypervascularization in injured shoulders. In vitro, gain of miR-29a function attenuated COL3A1 expression through binding to the 3'-untranslated region (3'-UTR) of COL3A1 in inflamed tenocytes, whereas silencing miR-29a increased the matrix expression. Taken together, miR-29a loss is correlated with subacromial bursa inflammation and fibrosis in rotator cuff tear with shoulder stiffness. miR-29a repressed subacromial bursa fibrosis through directly targeting COL3A1 mRNA, improving rotator cuff integrity and shoulder function. Collective analysis offers a new insight into the molecular mechanism underlying rotator cuff tear with shoulder stiffness. This study also highlights the remedial potential of miR-29a precursor for alleviating the shoulder disorder.

S100 Calcium Binding Protein A9 Represses Angiogenic Activity and Aggravates Osteonecrosis of the Femoral Head.

Ischemic damage aggravation of femoral head collapse is a prominent pathologic feature of osteonecrosis of the femoral head (ONFH). In this regard, S100 calcium binding protein A9 (S100A9) is known to deteriorate joint integrity, however, little is understood about which role S100A9 may play in ONFH. In this study, a proteomics analysis has revealed a decrease in the serum S100A9 level in patients with ONFH upon hyperbaric oxygen therapy. Serum S100A9 levels, along with serum vascular endothelial growth factor (VEGF), soluble vascular cell adhesion molecule-1 (sVCAM-1), interleukin-6 (IL-6), and tartrate-resistant acid phosphatase 5b levels were increased in patients with ONFH, whereas serum osteocalcin levels were decreased as compared to healthy controls. Serum S100A9 levels were increased with the Ficat and Arlet stages of ONFH and correlated with the patients with a history of being on glucocorticoid medication and alcohol consumption. Osteonecrotic tissue showed hypovasculature histopathology together with weak immunostaining for vessel marker CD31 and von Willrbrand factor (vWF) as compared to femoral head fracture specimens. Thrombosed vessels, fibrotic tissue, osteocytes, and inflammatory cells displayed strong S100A9 immunoreactivity in osteonecrotic lesion. In vitro, ONFH serum and S100A9 inhibited the tube formation of vessel endothelial cells and vessel outgrowth of rat aortic rings, whereas the antibody blockade of S100A9 improved angiogenic activities. Taken together, increased S100A9 levels are relevant to the development of ONFH. S100A9 appears to provoke avascular damage, ultimately accelerating femoral head deterioration through reducing angiogenesis. This study provides insight into the molecular mechanism underlying the development of ONFH. Here, analysis also highlights that serum S100A9 is a sensitive biochemical indicator of ONFH.

MicroRNA-29a Counteracts Glucocorticoid Induction of Bone Loss through Repressing TNFSF13b Modulation of Osteoclastogenesis.

Glucocorticoid excess escalates osteoclastic resorption, accelerating bone mass loss and microarchitecture damage, which ramps up osteoporosis development. MicroRNA-29a (miR-29a) regulates osteoblast and chondrocyte function; however, the action of miR-29a to osteoclastic activity in the glucocorticoid-induced osteoporotic bone remains elusive. In this study, we showed that transgenic mice overexpressing an miR-29a precursor driven by phosphoglycerate kinase exhibited a minor response to glucocorticoid-mediated bone mineral density loss, cortical bone porosity and overproduction of serum resorption markers C-teleopeptide of type I collagen and tartrate-resistant acid phosphatase 5b levels. miR-29a overexpression compromised trabecular bone erosion and excessive osteoclast number histopathology in glucocorticoid-treated skeletal tissue. Ex vivo, the glucocorticoid-provoked osteoblast formation and osteoclastogenic markers (NFATc1, MMP9, V-ATPase, carbonic anhydrase II and cathepsin K) along with F-actin ring development and pit formation of primary bone-marrow macrophages were downregulated in miR-29a transgenic mice. Mechanistically, tumor necrosis factor superfamily member 13b (TNFSF13b) participated in the glucocorticoid-induced osteoclast formation. miR-29a decreased the suppressor of cytokine signaling 2 (SOCS2) enrichment in the TNFSF13b promoter and downregulated the cytokine production. In vitro, forced miR-29a expression and SOCS2 knockdown attenuated the glucocorticoid-induced TNFSF13b expression in osteoblasts. miR-29a wards off glucocorticoid-mediated excessive bone resorption by repressing the TNFSF13b modulation of osteoclastic activity. This study sheds new light onto the immune-regulatory actions of miR-29a protection against glucocorticoid-mediated osteoporosis.

Extracorporeal shockwave therapy for treatment of keloid scars.

The purpose of this investigation was to study the effectiveness of extracorporeal shockwave therapy (ESWT) for the treatment of keloid scars, and compared the results with intralesional steroid injection. Thirty-nine patients were randomly divided into 22 in ESWT group and 17 in steroid group. The ESWT group received 3 ESWT treatments in 6 weeks. The steroid group received three intra-lesional triamcinolone injections in 6 weeks. The evaluations included gross morphology, functional outcome, local blood flow perfusion, biopsy for histopathological examination, and immunohistochemical analysis. Both groups showed significant improvements in appearance with less discoloration, flattening and softer consistency, and more elasticity of the lesions. There is a significant reduction in keloid height after treatment in both groups, and significant differences are noticed between two groups after treatment. The volume of keloid was decreased after treatment but there is no statistically significant difference between two groups. Both groups showed comparable functional scores, POSAS patient, and observer scales. The blood flow perfusion rates were statistically not significant between two groups before and after treatments. Histopathological findings revealed no significant difference in cell count, cell activity, and cell concentration between two groups. After ESWT, the significant decreases in collagen type I, type III, and Masson Trichrome stain were observed as compared with steroid group. However, very little changes were noticed in angiogenesis, inflammatory cytokines, proliferating and regeneration, and apoptosis, with no statistical significance noticed between two groups before and after treatment. This study revealed that ESWT showed comparable functional outcome and POSAS patient and observer scales as compared with steroid injection for keloid scars. Treatment of keloid scars with ESWT resulted in significant decreases in collagen fibers and increases in MMP-13 enzyme.

Increased expression of type 1 cannabinoid (CB1) receptor among patients with rotator cuff lesions and shoulder stiffness.

BACKGROUND: Shoulder stiffness is a disease manifested by pain, limited range of motion, and functional disability. The inflammatory and fibrosis processes play a substantial role in the pathogenesis of shoulder stiffness. The CB1 receptor has been recognized to mediate the processes of pathologic fibrosis. This study investigated the role of the CB1 pathway in pathogenesis of rotator cuff lesions with shoulder stiffness. METHODS: All of the patients undergoing repair surgery for rotator cuff lesions were recruited and subcategorized into subjects with and without shoulder stiffness. Reverse transcription-polymerase chain reaction assay was used to evaluate the expression level of CB1 and interleukin 1ß (IL-1ß) in the subacromial bursae, and enzyme-linked immunosorbent assay was used to measure the concentration of CB1 and IL-1ß in the subacromial fluid. Tenocytes treated with CB1 agonists and antagonists were also studied for the relationship of CB1 and the inflammatory cytokine IL-1ß. RESULTS: The patients with shoulder stiffness had higher messenger RNA (mRNA) expression (P = .040) and immunohistochemistry staining (P < .001) of CB1 in the subacromial bursa and higher CB1 concentration in the subacromial fluid (P = .008). Tenocytes treated with the CB1 agonist WIN 55,212-2 and antagonist AM251 showed increased expression of IL-1ß mRNA (P = .049) and suppressed expression of IL-1ß mRNA (P = .001), respectively. DISCUSSION: The CB1 pathway is involved in the pathogenesis of shoulder stiffness. It may be a promising target for the treatment of rotator cuff lesions with shoulder stiffness.

Predictors of Treatment Failure After 2-Stage Reimplantation for Infected Total Knee Arthroplasty: A 2- to 10-Year Follow-Up.

BACKGROUND: The aim of this study is to identify risk factors which may lead to treatment failure following 2-stage reimplantation for chronic infected total knee arthroplasty (TKA). METHODS: We retrospectively reviewed 106 patients (108 knees) who underwent consecutive 2-stage revision for chronic PJI of the knee at our institution between January 2005 and December 2015. A total of 31 risk factors, including patient characteristics, comorbidities, surgical variables, and microbiology data, were collected. Kaplan-Meier survival and Cox regression analyses were used to calculate survival rates and adjusted hazard ratios (HRs) of treatment failure. RESULTS: Within the cohort, 16 of the 108 2-stage reimplantations (14.8%) had treatment failure. The treatment success for 2-stage reimplantation was 91% (95% confidence interval [CI] 0.8-1.0) at 2 years and 84% (95% CI 0.8-0.9) at 5 and 10 years. Multivariate analysis provided the strongest predictors of treatment failure, including body mass index ≥30 kg/m2 (adjusted HR 9.3, 95% CI 2.7-31.8, P < .001), operative time >4 hours (adjusted HR 11.3, 95% CI 3.9-33.1, P < .001), gout (adjusted HR 13.8, 95% CI 2.9-66.1, P = .001), and the presence of Enterococcus species during resection arthroplasty (adjusted HR 14.1, 95% CI 2.6-76.3, P = .002). CONCLUSION: Our study identified 4 potential risk factors that may predict treatment failure following 2-stage revision for chronic knee PJI. This finding may be useful when counseling patients regarding the treatment success and prognosis of 2-stage reimplantation for infected TKA.