Transcription Factor KLF7 Promotes Osteoclast Differentiation by Suppressing HO-1.

Background: Osteoporosis is a common orthopedic disease with high prevalence in patients older than 50 years. Osteoporosis is often detected only after the fracture and is hard to treat. Therefore, it is of great significance to explore the molecular mechanism of the occurrence of osteoporosis. Methods: The expression of Heme oxygenase-1 (HO-1) in people with different bone mineral density (BMD) was analyzed based on public databases. GenHacncer and JASPAR databases were adopted to search and verify the upstream transcription factor of HO-1. qRT-PCR, western blot and tartrate-resistant acid phosphatase assays were performed to explore the impact of HO-1 and Kruppel-like factor 7 (KLF7) on osteoclast differentiation. Chromatin immunoprecipitation (ChIP) assay confirmed the binding relationship between KLF7 and HO-1. Finally, Hemin, the agonist of HO-1, was applied in rescue assays, thereby verifying the mechanism of KLF7 modulating osteoclast differentiation by HO-1. Results: Bioinformatics analysis revealed that HO-1 was highly-expressed while KLF7 lowly-expressed in people with high BMD. Besides, a potential binding site of KLF7 was found on the promoter region of HO-1. ChIP assay further manifested the targeting relationship between HO-1 and KLF7. Western blot and TRAP staining unveiled that osteoclast differentiation was suppressed by HO-1, while facilitated by KLF7. Rescue experiments indicated that over-expressed HO-1 could reverse of the promoting effect of KLF7 on osteoclast differentiation. Conclusion: The study confirmed that osteoclast differentiation was promoted by KLF7 constraining HO-1, thereby facilitating osteoporosis. The cognation of the pathogenesis of osteoporosis was further enriched. New treatment could be developed on this basis.

Circular RNA circ_0000020 promotes osteogenic differentiation to reduce osteoporosis via sponging microRNA miR-142-5p to up-regulate Bone Morphogenetic Protein BMP2.

This study was designed to study functions of Circ_0000020 during osteogenic differentiation. First, we used RT-qPCR to detect the expression of Circ_0000020, miR-142-5p and osteogenesis-related genes, whereas western blot analysis detected the expression of osteogenesis markers after the osteogenic differentiation of primary BMSCs isolated from rats. Alkaline phosphatase (ALP) activity and alizarin red Sstaining validated osteoblast phenotypes. Flow cytometry was used to detect cell apoptosis. Sh-Circ_0000020 was used to study the function of Circ_0000020 in osteogenic differentiation of BMSCs. Luciferase assay and RNA immunoprecipitation were used to validate the interaction between Circ_0000020 and miR-142-5p, and BMP2 and miR-142-5p. Co-transfection of miR-142-5p and sh-Circ_0000020 was used to verify the downstream signaling pathway. Circ_0000020 expression was up-regulated during osteogenic differentiation, whereas miR-142-5p expression was significantly decreased. Silencing Circ_0000020 inhibited osteogenic differentiation and promoted apoptosis, and inhibited ALP activity and mineralization ability. Moreover, Circ_0000020 interacts directly with miR-142-5p which binds to the BMP2 3'UTR and inhibits its expression. Additionally, co-transfection of miR-142-5p inhibitors and sh-Circ_0000020 rescued down-regulated BMP2, increased the expression osteogenesis-related gene expressions, and thereby rescued the inhibition of osteogenic differentiation induced by Circ_0000020 silencing. Furthermore, co-transfection of miR-142-5p inhibitors and sh-Circ_0000020 reversed Circ_0000020 silencing-induced downregulation of p-Smad1/5/8, Runx2, and Osterix protein levels. Circ_0000020 regulates BMP2 expression through sponging miR-142-5p as ceRNA, thereby positively regulating BMSCs osteogenic differentiation through Circ_0000020/miR-142-5p/BMP2/SMAD-dependent signaling pathway.

Efficacy of volar and dorsal plate fixation for unstable dorsal distal radius fractures.

OBJECTIVE: To compare the efficacy of volar and dorsal plate fixation for unstable dorsal distal radius fractures. METHODS: Forty-seven cases were selected from patients undergoing surgical reduction and internal fixation treatment in our hospital from August 2006 to October 2010, with 21 males and 26 females, aged 39-73 years old. Patients were divided into two groups: volar plate fixation group (Group A) which has 32 cases, including 27 cases with locking plate, 5 cases with ordinary T plate, and 4 cases combined with dorsal Kirschner wire fixation; dorsal plate fixation group (Group B) which has 15 cases, including 7 cases with locking plate. The efficacy of the two fixation methods were compared in terms of postoperative wrist function, X-ray score, and postoperative complications. RESULTS: Compared with those of preoperative groups, the volar tilt, ulnar deviation and radial styloid height in both group A and B were significantly improved one week after surgery as shown by X-ray imaging. Comparison of X-ray images one week after surgery with those of six months after surgery showed no significant changes in volar tilt, ulnar deviation or radial styloid height. 87.5% of patients in group A and 86.7% of patients in group B got "excellent" in their wrist function assessment, and there was no significant difference between the two groups (X(2)=0.825, P=1.000). But patients in group A hax significantly lower incidence rate of postoperative complications than group B (X(2)=4.150, P=0.042). CONCLUSION: For unstable distal radius fractures with dorsal displacement, volar plate fixation can achieve satisfactory reduction results, and cause less tendon damage or other complications than dorsal plate fixation.

Effects of hook plate on shoulder function after treatment of acromioclavicular joint dislocation.

INTRODUCTION: Internal fixation with hook plate has been used to treat acromioclavicular joint dislocation. This study aims to evaluate the effect of its use on shoulder function, to further analyze the contributing factors, and provide a basis for selection and design of improved internal fixation treatment of the acromioclavicular joint dislocation in the future. METHODS: A retrospective analysis was performed on patients treated with a hook plate for acromioclavicular joint dislocation in our hospital from January 2010 to February 2013. There were 33 cases in total, including 25 males and 8 females, with mean age of 48.27 ± 8.7 years. There were 29 cases of Rockwood type III acromioclavicular dislocation, 4 cases of type V. The Constant-Murley shoulder function scoring system was used to evaluate the shoulder function recovery status after surgery. Anteroposterior shoulder X-ray was used to assess the position of the hook plate, status of acromioclavicular joint reduction and the occurrence of postoperative complications. RESULTS: According to the Constant-Murley shoulder function scoring system, the average scores were 78 ± 6 points 8 to 12 months after the surgery and before the removal of the hook plate, the average scores were 89 ± 5 minutes two months after the removal of hook plate. Postoperative X-ray imaging showed osteolysis in 10 cases (30.3%), osteoarthritis in six cases (18.1%), osteolysis associated with osteoarthritis in four cases(12.1%), and steel hook broken in one case (3%). CONCLUSION: The use of hook plate on open reduction and internal fixation of the acromioclavicular joint dislocation had little adverse effect on shoulder function and is an effective method for the treatment of acromioclavicular joint dislocation. Osteoarthritis and osteolysis are the two common complications after hook plate use, which are associated with the impairment of shoulder function. Shoulder function will be improved after removal of the hook plate.

Hispidulin exerts anti-osteoporotic activity in ovariectomized mice via activating AMPK signaling pathway.

To investigate the effect of Hispidulin on ovariectomy (OVX)-induced bone loss in mice. Female mice subjected to OVX were treated with Hispidulin for 8 weeks. The total body bone mineral density was measured at the beginning and after the OVX at a time interval of 4 weeks. Micro-computed tomography of the tibia, bone histomorphometric analysis of the femur, and biomechanical analysis of tibia, vertebra, and femoral head were performed to fully evaluate the anti-osteoporotic effect of Hispidulin. Western blot analysis was performed to determine the level of activated AMPK. Hispidulin treatment effectively prevented OVX-induced body weight loss and attenuated OVX-induced bone loss. Hispidulin treatment also decreased trabecular spacing in OVX mice. The suppressing effect of Hispidulin on osteoclast surface and number was also found via histomorphometric analysis. Western blot analysis revealed that Hispidulin significantly elevated the activated AMPK levels. Our findings suggest that Hispidulin exerts anti-osteoporotic and bone resorption attenuating effects via activating the AMPK signaling pathway.

[Case-control study on volar and dorsal plate for the treatment of dorsal unstable distal radius fractures].

OBJECTIVE: To investigate the internal fixation methods in the two different surgical approach to the unstable distal radius fractures. METHODS: From August 2006 to October 2010,47 patients with distal radius fractures were treated with open reduction and plate internal fixation. Among the patients, 21 patients were male and 26 patients were female,ranging in age from 39 to 73 years old. All the patients were divided into two groups: 32 patients were treated with plate fixation at the palm side with palm side incision (group A),including locking plate used in 27 patients and ordinary T shape plate used in 5 patients; 15 patients were treated with dorsal plate fixation (group B), including locking plate used in 7 patients and ordinpry T shape plate used in 8 patients. The postoperative wrist function, X-ray score,complications were compared between the two groups. RESULTS: Compare to preoperative, postoperative volar tilt,ulnar deviation and radial styloid height of both groups improved; and comparison between 1 week after operation and 6 months after operation,volar tilt,ulnar deviation and radial styloid height of both groups had no obvious loss. In group A, 1 patient had tension injury of median nerve, 1 patient had incision infection, 2 patients had adhesion of tendon; and in group B,1 patient had incision swelling and infection, 1 patient had adhesion of tendon,3 patients had stimulation of extensor pollicis longus muscle tendon. The complication occurrence rate of group A is lower than that of group B. The wrist functional assessment: 17 patients got an excellent results, 11 good, 3 poor and 1 bad in group A; and 8 excellent, 4 good, 2 poor and 1 bad in group B. There was no statistically significant difference of wrist function between the two groups. CONCLUSION: Plate fixation at the palm side for the treatment of unstable distal radius fractures can also achieve a good reduction,and has less complication such as tendon damage than that of dorsal plate fixation.