Retraction: Strontium-doped gelatin scaffolds promote M2 macrophage switch and angiogenesis through modulating the polarization of neutrophils.

Retraction of 'Strontium-doped gelatin scaffolds promote M2 macrophage switch and angiogenesis through modulating the polarization of neutrophils' by Tao Li et al., Biomater. Sci., 2021, 9, 2931-2946, https://doi.org/10.1039/D0BM02126A.

The BRD4-SRPK2-SRSF2 signal modulates the splicing efficiency of ACSL3 pre-mRNA and influences erastin-induced ferroptosis in osteosarcoma cells.

Lipid metabolism is the key to ferroptosis susceptibility. However, little is known about the underlying mechanisms in osteosarcoma cells. Functional restriction of bromodomain-containing protein 4 (BRD4) reduced the susceptibility to erastin-induced ferroptosis of osteosarcoma cells both in vitro and in vivo. Mechanically, BRD4 controls the splicing efficiency of the RNA precursor (pre-mACSL3) of ACSL3 (ACSL3) by recruiting serinerich/threonine protein kinase 2 (SRPK2) to assemble the splicing catalytic platform. Moreover, the AMP-binding domain of ACSL3 significantly influences arachidonic acid synthesis and thus determines the susceptibility to erastin-induced ferroptosis. Overall, we found a BRD4-mediated pre-mACSL3 splicing influences erastin-induced ferroptosis by affecting arachidonic acid synthesis in osteosarcoma cells. Data in this study fills some of the gap in understanding the post-transcriptional regulatory mechanisms of ACSL3 and provides new insights into the mechanisms of lipid metabolism regulation and its effect on susceptibility to ferroptosis in osteosarcoma cells.

Epidemiological updates of post-traumatic related limb osteomyelitis in china: a 10 years multicentre cohort study.

BACKGROUND: Post-traumatic related limb osteomyelitis (PTRLO) is a complex bone infection. Currently, there are no available microbial data on a national scale that can guide appropriate antibiotic selection, and explore the dynamic changes in dominant pathogens over time. This study aimed to conduct a comprehensive epidemiological analysis of PTRLO in China. METHODS: The study was approved by the Institutional Research Board (IRB), and 3526 PTRLO patients were identified from 212 394 traumatic limb fracture patients at 21 hospitals between 1 January 2008 and 31 December 2017. A retrospective analysis was conducted to investigate the epidemiology of PTRLO, including changes in infection rate (IR), pathogens, infection risk factors and antibiotic resistance and sensitivity. RESULTS: The IR of PTRLO increased gradually from 0.93 to 2.16% (Z=14.392, P <0.001). Monomicrobial infection (82.6%) was significantly higher than polymicrobial infection (17.4%) ( P <0.001). The IR of Gram-positive (GP) and Gram-negative (GN) pathogens showed a significant increase from the lowest 0.41% to the highest 1.15% (GP) or 1.62% (GN), respectively. However, the longitudinal trend of GP vs. GN's composition did not show any significance (Z=±1.1918, P >0.05). The most prevalent GP strains were Methicillin-sensitive Staphylococcus aureus (MSSA) (17.03%), Methicillin-resistant Staphylococcus aureus (MRSA) (10.46%), E. faecalis (5.19%) and S. epidermidis (4.87%). In contrast, the dominant strains GN strains were Pseudomonas Aeruginosa (10.92%), E. cloacae (10.34%), E. coli (9.47%), Acinetobacter Baumannii (7.92%) and Klebsiella Pneumoniae (3.33%). In general, the high-risk factors for polymicrobial infection include opened-fracture (odds ratio, 2.223), hypoproteinemia (odds ratio, 2.328), and multiple fractures (odds ratio, 1.465). It is important to note that the antibiotics resistance and sensitivity analysis of the pathogens may be influenced by complications or comorbidities. CONCLUSIONS: This study provides the latest data of PTRLO in China and offers trustworthy guidelines for clinical practice. (China Clinical Trials.gov number, ChiCTR1800017597).

HMGB1 can activate cartilage progenitor cells in response to cartilage injury through the CXCL12/CXCR4 pathway.

INTRODUCTION: Recent studies have suggested that cartilage progenitor cells (CPCs) could be activated and differentiated into chondrocytes to produce matrix and to restore the integrity of damaged cartilage after injury. However, the mechanism involved in CPC activation upon damage is still unclear. This study aims to investigate the role of high mobility group box chromosomal protein 1 (HMGB1) in both activation and migration of CPCs during cartilage injury. MATERIAL AND METHODS: Explants harvested from mature bovine stifle joints were used for impact injury. The proliferation and migration of CPCs were examined via confocal imaging. Gene and protein expression of Hmbg1, Cxcl12, and Cxcr4 was also examined by quantitative polymerase chain reaction (qPCR), ELISA, and western blot. Each experiment was repeated 3 times. ANOVA and Student's t-test were performed for statistical analysis. RESULTS: HMGB1 released from dead and damaged chondrocytes after an impact injury could activate CPCs in the superficial zone of cartilage and promote their migration and proliferation to injury sites. However, the block of HMGB1 activation with its specific binding inhibitor glycyrrhizin inhibits the proliferation and migration of CPCs. Further investigations demonstrate that HMGB1 promotes CPCs migration through the pathway of C-X-C motif chemokine 12 (CXCL12) and its receptor CXCR4. Quantitative analysis of HMGB1 in cell culture medium also indicates that CPCs may have a self-activation property after the HMGB1 released from dead cells has been exhausted. CONCLUSION: HMGB1 is a pivotal factor that could enhance the migration and proliferation of CPCs through the CXCL12/CXCR4 pathway after cartilage injury, which could provide useful information for cartilage repair and osteoarthritis treatment.

Overexpression of Wnt7b antagonizes the inhibitory effect of dexamethasone on osteoblastogenesis of ST2 cells.

INTRODUCTION: It is well established that glucocorticoid-induced osteoporosis is highly associated with preosteoblast differentiation and function. This study is based on the premise that Wnt7b can promote bone formation through Wnt signalling pathway because it can stimulate preosteoblast differentiation and increase its activity. However, it is unknown whether Wnt7b can rescue the inhibited osteoblast differentiation and function caused by exogenous glucocorticoid. MATERIAL AND METHODS: In this study we used Wnt7b overexpression ST2 cells to explore whether Wnt7bcan rescue the inhibited osteoblast differentiation and function, which can provide strong proof to investigate a new drug for curing the glucocorticoid induced osteoporosis. RESULTS/CONCLUSION: We found that Wnt7b can rescue the suppressed osteoblast differentiation and function without cell viability caused by dexamethasone.

Distally Based Sural Fasciocutaneous Flaps for Reconstructing Soft Tissue Defects Proximal and Distal to the Tarsometatarsal Joints: A Comparative Analysis.

Distally based sural fasciocutaneous (DBSF) flaps are widely used for reconstructing soft tissue defects of the foot. The purpose of this paper was to compare the clinical efficacy of the use of flaps to repair defects in areas proximal and distal to the level of the tarsometatarsal joints in a relatively large number of patients and to analyze the effects of factors on the risk of developing partial necrosis of the flaps. Between April 2001 and December 2019, a total of 355 DBSF flaps were utilized to cover soft tissue defects in the foot. According to the furthest location of the defects reconstructed with the flaps, the flaps were divided into the proximal foot group (n = 260) and the distal foot group (n = 95). The partial necrosis rates, their influencing factors, and the clinical outcomes of the procedure were compared between the two groups. In the proximal foot group, the partial necrosis rate (6.2%, 16 of 260) was significantly lower than that in the distal foot group (14.7%, 14 of 95) (P < .05). The proportion of successful coverage of the defects using the flaps alone or in combination with a simple salvage treatment was comparable between the groups (P > .05). The ratio of unfavorable conditions in the distal foot group was higher than that in the proximal foot group (P < .05). DBSF flaps can be effectively utilized to repair defects in the proximal and distal areas of the foot. The use of a DBSF flap to repair defects in the proximal areas of the foot is superior to the use of DBSF flaps for repairing defects in the distal areas of the foot in terms of reliable survival of the flap.

Three-Dimensional Printing Model Enhances Correct Identification and Understanding of Pelvic Fracture in Medical Students.

OBJECTIVE: Understanding the anatomy behind a pelvic fracture can be a significant challenge to medical students. Recent advances in three-dimensional printing technology offers a novel approach to facilitate the learning of complex fracture. We have described here how the 3-dimension printing (3Dp) models can help medical students improve their understanding in and identification of pelvic fractures. DESIGN: One hundred students were randomized into 2 teaching module groups (with or without 3Dp models). Prior to randomization assignment, a 50-minute didactic lecture covering elementary knowledge of anatomy, Young-Burgess classification, and traumatic mechanism of pelvic fracture was delivered to all students. The 3Dp group received X-rays, CT images, and 3Dp models of the eight pelvic fractures during presentation, while the students in the control group only obtained X-rays and CT scans of the same 8 pelvic fractures. Young-Burgess classification system and injury mechanism of pelvic fracture, time for evaluation, and subjective questions were conducted to assess the learning outcomes. SETTING: A medical student program based in a LevelⅠtrauma center PARTICIPANTS: One hundred students in their 4th year of a 5-year clinical medicine program (for a medical bachelor degree) RESULTS: Students receiving 3Dp model had a higher rate of identifying the correct pelvic fracture via Young-Burgess identification compared to these without 3Dp model. Moreover, the accuracy of identifying the injury mechanism was significantly higher in the 3Dp group than that in group without 3Dp model. Participant in 3Dp group had faster assessment time compared to the control group. Subjective survey results suggested that 3Dp model would increase the learning interest and enhance the understanding of pelvic fracture. In addition, majority of students (83%) reported that they would like to use 3Dp model in other surgical course education. CONCLUSIONS: 3Dp model increased the perceived accuracy of pelvic fracture identification and understanding of injury mechanism. Moreover, 3Dp model promoted the subjective interest and motivation of students in pelvic fracture learning. Therefore, 3Dp model can be considered as a valuable educational tool for learning pelvic fracture in medical students.

Efficacy and safety of platelet-rich plasma combined with hyaluronic acid versus platelet-rich plasma alone for knee osteoarthritis: a systematic review and meta-analysis.

PURPOSE: To systematically evaluate the curative efficacy and safety of platelet-rich plasma (PRP) combined with hyaluronic acid (HA) in the treatment of knee osteoarthritis (KOA), comparing with platelet-rich plasma alone. METHODS: Cochrane Library, PubMed, China National Knowledge Infrastructure (CNKI) and Embase were searched for randomized controlled trials (RCTs) and cohort studies regarding the efficacy and safety of platelet-rich plasma (PRP) combined with hyaluronic acid (HA) in the treatment of knee osteoarthritis (KOA) comparing with platelet-rich plasma alone before January 15, 2022. The methodological quality of the ultimately included studies was assessed comprehensively, and meta-analysis was implemented using RevMan 5.3 software. RESULTS: Thirteen articles (9 RCTs, 4 cohort studies), including 1118 patients, were covered. There was no significant difference between the PRP + HA therapy and PRP-alone therapy in VAS scores at 3 months, 6 months and 12 months, WOMAC total scores at 3 months and KOOS at 1 month and 6 months. Compared with PRP-alone therapy, PRP + HA therapy was associated with significantly better improvement in VAS scores at 1 month, WOMAC total scores at 6 months, KOOS at 3 months, IKDC scores at 6 months and Lequesne index scores at 3 and 6 months. However, the smallest treatment effect of VAS scores, WOMAC total scores, KOOS and IKDC scores did not exceed the minimum clinically important difference (MCID). However, PRP + HA therapy got a greater reduction in the rate of adverse events, compared with PRP-alone therapy. CONCLUSION: The results of this meta-analysis indicated that PRP + HA therapy was not found to be superior to PRP-alone therapy in pain relief and function improvement for patients with KOA. However, combined PRP with HA injections was generally safer than PRP injections alone, by assessing the incidence of adverse events.

Biomechanical study on parallel cannulated compression screw combined with medial buttress plate fixation and F-type cannulated compression screw fixation in Pauwels III femoral neck fracture：A finite element analysis. / å¹³è¡Œç©ºå¿ƒåŠ åŽ‹èžºé’‰è”åˆå† ä¾§æ”¯æ’‘é’¢æ¿ä¸ŽFåž‹ç©ºå¿ƒåŠ åŽ‹èžºé’‰å›ºå®šPauwels IIIåž‹è‚¡éª¨é¢ˆéª¨æŠ˜ç”Ÿç‰©åŠ›å­¦ç‰¹æ€§çš„æœ‰é™å ƒåˆ†æž.

OBJECTIVES: Pauwels III fracture is a kind of femoral neck fractures, in which the angle of the fracture line in the coronal plane and the upper edge of the acetabulum is more than 50°. Internal fixation for the treatment of femoral neck fractures is largely performed by cannulated compression screw (CCS), dynamic hip screw, or locking plate. This study aims to compare the biomechanical properties of parallel CCS combined with medial buttress plate fixation and F-type CCS fixation in the treatment of Pauwels III femoral neck fracture by finite element modeling and to determinate the most suitable procedure for such fractures. METHODS: A 52-year-old male volunteer, 176 cm in height and 72 kg in weight, with no history of hip joint, was selected. X-ray and CT examination confirmed that the morphology and bone condition of the right hip of the volunteer were normal. A simulation model of Pauwels III femoral neck fracture was established from the collected CT data of the right proximal femur of the volunteer by the finite element method. Four internal fixations were developed to treat the finite element model: Three CCSs in an inverted triangular parallel configuration combined with medial buttress plate model served as Group A, 2 CCSs in a vertical parallel configuration combined with medial buttress plate model served as Group B, 2 CCSs in a horizontal parallel configuration combined with medial buttress model served as Group C, and the "F" shaped CCS model served as Group D. The distribution of stress, the peak stress, the distribution and maximum of displacement of internal fixations and fracture ends in different models were evaluated. RESULTS: For Groups A, B, C, and D, the peak stresses on the internal fixation were 362.74, 586.84, 558.25, and 208.66 mPa, respectively, all of which occurred near the fractures and the stress distribution in Group D was the most uniform. The maximum displacements of internal fixations in Groups A, B, C, and D were 0.39, 0.45, 0.44, and 0.41 mm, respectively; the peak stresses on the fracture ends were 70.62, 98.48, 55.84, and 65.39 mPa, respectively, all of which were concentrated on the base of femoral neck and lateral cortex of the femoral shaft, and the stresses of Groups C and D were more evenly distributed than those of Groups A and B. The maximum displacements of fracture ends in Groups A, B, C, and D were 0.44, 0.52, 0.50, and 0.44 mm, respectively. CONCLUSIONS: The biomechanical stability of F-type CCS fixation is similar to that of 3 CCSs in an inverted triangular parallel configuration combined with medial buttress plate, with a better dispersion of stress. F-type CCS fixation may be a well option for the treatment of femoral neck fracture of Pauwels III.

Single Modified Posterior Approach through the Space of the Proximal Radioulnar Joint for Terrible Triad Injury: A Comparative Study.

OBJECTIVE: In order to reduce surgical scars and the risk of neurovascular injury for the treatment of terrible triad injuries of the elbow (TTI), minimally invasive and better therapeutic effect approaches are being explored to replace the conventional combined lateral and medial approach (CLMA). This study was performed to compare the clinical effect and security of the modified posterior approach (MPA) through the space of the proximal radioulnar joint vs the CLMA for treatment of TTI. METHODS: This study retrospectively analyzed 76 patients treated for TTI from January 2009 to December 2020 (MPA: n = 44; CLMA: n = 32). Treatment involved plate and screw fixation or Steinmann pin fixation for the radial head and ulnar coronoid process fractures. Surgeons only sutured the lateral ligament because the medial collateral ligament was usually integrated in the TTI. The continuous variables were compared by the independent Student t-test and the categorical variables by the χ2 -test or Fisher's exact test. RESULTS: Both groups of patients attained a satisfactory MEPS after the operation. The MEPS (MPA: 96.82 ± 6.04 vs CLMA: 96.56 ± 5.51) was not significantly different between the two groups (p > 0.05). However, the MPA resulted in better elbow flexion and extension (MPA: 123.98 ± 10.09 vs CLMA: 117.66 ± 8.29), better forearm rotation function (MPA: 173.41 ± 6.81 vs CLMA: 120.00 ± 12.18), and less intraoperative hemoglobin (MPA: 9.34 ± 5.64 vs CLMA: 16.5 ± 8.75) and red cell volume loss (MPA: 3.09 ± 2.20 vs CLMA: 6.70 ± 2.97) (All p < 0.05). Although the CLMA had a shorter surgery time (MPA: 171.73 ± 80.68 vs CLMA: 130.16 ± 71.50) (p < 0.05), it had a higher risk of neurologic damage (MPA: 0 vs CLMA: 4) (p < 0.05). Four patients developed forearm or hand numbness after the CLMA, but no patients developed numbness after the MPA. All 76 patients were followed up for 15 months postoperatively. CONCLUSION: The MPA through the space of the proximal radioulnar joint has more prominent advantages than the CLMA for TTI, including single scar, clear exposure, good fixation, lower risk of neurovascular injury, and better elbow joint motion. It is a safe and effective surgical approach that is worthy of clinical promotion.

Reconstruction of congenital pseudarthrosis of the clavicle with a barrel-shaped mono-cortical iliac crest autograft: A case report.

BACKGROUND: Congenital pseudarthrosis of the clavicle (CPC) is a rare congenital entity with unresolved aetiology and pathogenesis. Nearly 250 cases have been reported to date. CPC is characterized by a definite defect in the mid-clavicle at birth and is usually diagnosed when the deformity becomes evident in late childhood or adolescence. Surgical management is controversial, especially in asymptomatic children, with various techniques reported in the literature. CASE REPORT: We report a case of a 6-year-old boy who was diagnosed with CPC during a medical examination for primary school enrollment. Operative treatment included debridement of pseudoarthrosis, internal fixation with third tube plate, and barrel-shaped mono-cortical iliac crest autograft. RESULTS: A complete bone union was obtained 9 months after the operation, and satisfactory function and cosmetic appearance were observed 4 years and 3 months postoperatively. CONCLUSION: In our opinion, reconstruction with barrel-shaped mono-cortical iliac crest autograft was an effective and reproducible surgical technique to treat CPC.

miR-122-5p targets GREM2 to protect against glucocorticoid-induced endothelial damage through the BMP signaling pathway.

Glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH) accounts for a big portion of non-traumatic ONFH; nevertheless, the pathogenesis has not yet been fully understood. GC-induced endothelial dysfunction might be a major contributor to ONFH progression. The Gene Expression Omnibus (GEO) dataset was analyzed to identify deregulated miRNAs in ONFH; among deregulated miRNAs, the physiological functions of miR-122-5p on ONFH and endothelial dysfunction remain unclear. In the present study, miR-122-5p showed to be under-expressed within GC-induced ONFH femoral head tissues and GC-stimulated bone microvascular endothelial cells (BMECs). In human umbilical vein endothelial cells (HUVECs) and BMECs, GC stimulation significantly repressed cell viability, promoted cell apoptosis and increased the mRNA expression of proinflammatory cytokines, such as TNF-α, IL-1ß, and IFN-γ. After overexpressing miR-122-5p, GC-induced endothelial injuries were attenuated, as manifested by rescued cell viability, cell migration, and tube formation capacity. Regarding the BMP signaling, GC decreased the protein levels of BMP-2/6/7 and SMAD-1/5/8, whereas miR-122-5p overexpression significantly attenuated the inhibitory effects of GC on these proteins. Online tool and experimental analyses revealed the direct binding between miR-122-5p and GREM2, a specific antagonist of BMP-2. In contrast to miR-122-5p overexpression, GREM2 overexpression aggravated GC-induced endothelial injury; GREM2 silencing partially eliminated the effects of miR-122-5p inhibition on GC-stimulated HUVECs and BMECs. Finally, GREM2 silencing reversed the suppressive effects of GC on BMP-2/6/7 and SMAD-1/5/8, and attenuated the effects of miR-122-5p inhibition on these proteins upon GC stimulation. Conclusively, the present study demonstrates a miR-122-5p/GREM2 axis modulating the GC-induced endothelial damage via the BMP/SMAD signaling. Considering the critical role of endothelial function in ONFH pathogenesis, the in vivo role and clinical application of the miR-122-5p/GREM2 axis is worthy of further investigation.

Distally Based Peroneal Artery Perforator-Plus Fasciocutaneous Flap to Reconstruct Soft Tissue Defect Combined With Chronic Osteomyelitis in the Lateral Malleolus.

Distally based peroneal artery perforator-plus fasciocutaneous (DPAPF) flaps are widely used to reconstruct soft tissue defects of the lower extremity. Treatment for soft tissue defect combined with chronic osteomyelitis in the lateral malleolus has rarely been reported. The aim of this study was to elaborate the superiority of the DPAPF flap and provide referential experience for using the DPAPF flap in this situation. Between June 2010 and December 2017, soft tissue defects in the setting of chronic osteomyelitis in the lateral malleolus were reconstructed with DPAPF flaps in 17 patients. After thorough debridement, the defect was repaired with the DPAPF flap, and patients subsequently followed an antibiotic regimen for 6 weeks. Follow-up periods for all patients were at least 24 months. The reconstruction outcomes and the satisfaction of the 17 patients were evaluated. Of the 17 flaps, 16 survived uneventfully, except one occurrence of partial necrosis. No infection occurred in the follow-up period. In the study, 17 patients except one were satisfied with flap appearance. All the patients were satisfied with the reconstruction outcomes. In a one-stage procedure, the use of DPAPF flaps is ideal for reconstructing soft tissue defects in the setting of chronic osteomyelitis in the lateral malleolus.

The Effect of Bisphosphonates on Fracture Healing Time and Changes in Bone Mass Density: A Meta-Analysis.

Background: Osteoporosis is a common complication of acute fracture, which can lead to fracture delayed union or other complications and resulting in poor fracture healing. Bisphosphate is a common anti-osteoporosis drug, but its application in fracture patients is still controversial because of its inhibitory effect on bone resorption. Method: Studies were acquired from literature databases in accordance with established inclusion criteria. Standard mean difference (SMD) and 95% confidence intervals (Cls) were calculated to evaluate the effectiveness of the bisphosphonates treatment in fracture patients. Data analysis was conducted with the Review Manager 5.4.1 software. Results: A total of 16 studies involving 5022 patients obtained from selected databases were examined. As expected, bisphosphate had no significant effect on fracture healing time, but it could significantly increase BMD and prevent osteoporosis. Meanwhile, bisphosphate can inhibit both bone resorption and bone formation markers, resulting in low bone turnover state. Conclusion: This meta-analysis showed that bisphosphonate have no significant effect on fracture healing time but they do increase the changes in BMD and reduce bone synthesis and resorption markers. Early application of bisphosphonates after injury in the appropriate patient population should be considered.

Old unreduced obturator dislocation of the hip: A case report.

BACKGROUND: Obturator dislocation is a rare type of hip dislocation, accounting for about 2%-5% of all hip dislocations. The occurrence of old unreduced obturator dislocation is even more infrequent, with only 17 cases reported in nine studies, most of which were from the 1950s to 1980s in developing countries. CASE SUMMARY: A 38-year-old woman from Hunan Province, China presented with stiffness of the left hip in abduction, flexion, and external rotation after falling from a 2-meter-tall tree onto her left knee 1.5 mo prior. Pelvic radiograph and computed tomography revealed obturator dislocation of the left hip accompanied by impaction fracture at the superolateral aspect of the left femoral head without associated acetabulum fracture. Open reduction was performed, resulting in restoration of the concentric alignment of the left hip. After surgery, 6-wk skin traction was applied and the patient was kept in bed for an additional 2 wk. At 3 mo after surgery, the patient reported experiencing some pain, which did not affect the function of the affected limb, and some movement restriction but no abduction deformity or claudication was present. An X-ray showed that the left hip was homocentric, and there was no sign of posttraumatic arthritis or avascular necrosis. CONCLUSION: Open reduction may be an effective treatment strategy for the rare condition of old unreduced obturator dislocation with short neglect time.

Functional interaction between Wnt and Bmp signaling in periosteal bone growth.

Wnt and Bmp proteins are well known to regulate bone development and homeostasis. Although both signals are extensively studied, their potential interaction in vivo is less well understood. Previous studies have shown that deletion of Bmpr1a, a type I receptor for Bmp signaling, results in excessive trabecular bone formation while diminishing periosteal bone growth. Moreover, forced-expression of the Wnt antagonist Sost suppresses the overgrowth of trabecular bone caused by Bmpr1a deletion, thus implicating hyperactive Wnt signaling in the excessive trabecular bone formation. However, it remains uncertain whether Wnt and Bmp signaling interacts in regulating the periosteal bone growth. Here we show that multiple Wnt genes are markedly suppressed in the cortical bone without Bmpr1a. Importantly, overexpression of Wnt7b fully rescues periosteal bone growth in the Bmpr1a-deficient mice. Thus, pharmacological activation of Wnt signaling can restore normal bone size without intact Bmp signaling.

Use of a Double Reverse Traction Repositor versus a Traction Table for the Treatment of Intertrochanteric Femur Fractures: A Comparative Study.

OBJECTIVE: The aim of the present study was to compare the clinical results for unstable femoral intertrochanteric fractures treated with a double reverse traction repositor (DRTR) and those treated using a traction table with the Asia proximal femoral nail antirotation (PFNA-II). METHODS: A retrospective study was performed including 95 patients with AO/OTA type 31-A2 and 31-A3 unstable femoral intertrochanteric fractures who underwent DRTR or traction table-facilitated PFNA-II nailing from April 2015 to December 2018 in our traumatic center. Demographics, duration of operation, blood loss, part loading time after surgery, fracture healing time, and early and late complications were assessed. Clinical and radiological outcomes were collected to compare the differences between the two groups. RESULTS: A total of 95 unstable intertrochanteric fracture patients treated with the PFNA-II were analyzed. Of these cases, 56 patients were treated with a DRTR and the other 39 patients were treated using a traction table to achieve fracture reduction. No patients died during surgery and hospitalization. There were no significant differences in respect to demographics and fracture characteristics of cases enrolled. The total operative time was significantly longer in the traction table group than in the DRTR group (72.5 ± 6.1 min for the traction table and 63.0 ± 4.1 min for the DRTR group, P < 0.001). No significant differences were observed in intraoperative blood loss and duration of hospitalization. The periods of follow up ranged from 12 to 31 months among all patients. At the last follow up, the Harris hip score (HHS) in the DRTR group was excellent in 10 patients (17.9%), good in 36 (64.3%), fair in 8 (14.3%), and poor in 2 (3.6%). These scores were comparable to those in the traction table group, which were: excellent in 8 patients (20.5%), good in 24 (61.5%), fair in 6 (15.4%), and poor in 1 (2.6%). Regarding the radiological evaluation, excellent rates of reduction rate were achieved in 39 cases (69.6%) in the DRTR group, which was comparable to 19 cases (48.7%) in the traction table group. In addition, the mean fracture healing time after surgery was 20.6 ± 2.3 weeks in the DRTR group and 21.4 ± 3.4 weeks in the traction table group, which did not reach a significant difference (P = 0.18). During the follow up, 6 cases of thigh pain, 4 cases of deep vein thrombosis, and 1 case of fracture of the anterior superior iliac spine were reported in the DRTR group. In the traction table group, there were 2 cases of deep vein thrombosis and 3 cases of thigh pain. CONCLUSION: When using the PFNA-II for unstable intertrochanteric fractures, the DRTR was superior to the traction table in respect to operative time and duration of patient position, despite an additional ipsilateral anterior superior iliac spine (ASIS) incision and drilling of the ASIS and the femur condyle.

miR-19b enhances osteogenic differentiation of mesenchymal stem cells and promotes fracture healing through the WWP1/Smurf2-mediated KLF5/ß-catenin signaling pathway.

Bone marrow mesenchymal stem cell (BMSC)-derived exosomes have been found to enhance fracture healing. In addition, microRNAs contributing to the healing of various bone fractures have attracted widespread attention in recent years, but knowledge of the mechanisms by which they act is still very limited. In this study, we clarified the function of altered microRNA-19b (miR-19b) expression in BMSCs in fracture healing. We modulated miR-19b expression via mimics/inhibitors in BMSCs and via agomirs in mice to explore the effects of these changes on osteogenic factors, bone cell mineralization and the healing status of modeled fractures. Through gain- and loss-of function assays, the binding affinity between miR-19b and WWP1/Smurf2 was identified and characterized to explain the underlying mechanism involving the KLF5/ß-catenin signaling pathway. miR-19b promoted the differentiation of human BMSCs into osteoblasts by targeting WWP1 and Smurf2. Overexpression of WWP1 or Smurf2 degraded the target protein KLF5 in BMSCs through ubiquitination to inhibit fracture healing. KLF5 knockdown delayed fracture healing by modulating the Wnt/ß-catenin signaling pathway. Furthermore, miR-19b enhanced fracture healing via the KLF5/ß-catenin signaling pathway by targeting WWP1 or Smurf2. Moreover, miR-19b was found to be enriched in BMSC-derived exosomes, and treatment with exosomes promoted fracture healing in vivo. Collectively, these results indicate that mesenchymal stem cell-derived exosomal miR-19b represses the expression of WWP1 or Smurf2 and elevates KLF5 expression through the Wnt/ß-catenin signaling pathway, thereby facilitating fracture healing.

Long non-coding RNA CIR inhibits chondrogenic differentiation of mesenchymal stem cells by epigenetically suppressing ATOH8 via methyltransferase EZH2.

BACKGROUND: Osteoarthritis (OA) is the most common articular disorder, leading to joint malfunction and disability. Although the incidence of OA is increasing globally, the treatment of OA is very limited. LncRNA CIR has been implicated in OA through unclear mechanisms. Here, we investigated the role of lncRNA CIR in chondrogenic differentiation. METHODS: Human umbilical-cord-derived mesenchymal stem cells (hUC-MSCs) were obtained from human umbilical cords. Flow cytometry was used to analyze the surface markers of hUC-MSCs. Various culture conditions and corresponding staining assays were employed to assess the differentiation abilities of hUC-MSC. qRT-PCR, western blot, and immunostaining were used to measure expression levels of related genes and proteins such as lncRNA CIR, ATOH8, EZH2, and H3K27me3. RNA immunoprecipitation assay, biotin pull-down, and chromatin immunoprecipitaion assay were performed to analyze the interactions of lncRNA CIR, EZH2, H3K27me3 and ATOH8 promoter. RESULTS: hUC-MSCs exhibited MSCs features and could differentiate into chondrocytes under specific conditions. LncRNA CIR was downregulated while ATOH8 was upregulated during the chondrogenic differentiation of hUC-MSCs. Knockdown lncRNA CIR or overexpression of ATOH8 promoted chondrogenic differentiation. Further, lncRNA CIR bound to EZH2 and repressed ATOH8 expression via EZH2-mediated H3K27me3, which promotes the methylation of ATOH8. Inhibition of ATOH8 reversed the effects of knockdown lncRNA CIR on chondrogenic differentiation. CONCLUSION: LncRNA CIR suppresses chondrogenic differentiation of hUC-MSCs. Mechanistically, lncRNA CIR could inhibit ATOH8 expression that functions to promote chondrogenic differentiation through EZH2-mediated epigenetic modifications.

Relationship between lipid metabolism and Hedgehog signaling pathway.

The Hedgehog (Hh) signaling pathway is highly conserved signaling pathway in cells. Steroids was found to play a vital role in Hh signaling pathway and aberrant Hh signaling was found to lead a series of disease correlate with abnormal lipid metabolism. This paper aimed to elucidate the relationship between lipid metabolism and Hedgehog signaling pathway.