USF2 reduces BMP3 expression via transcriptional activation of miR-34a, thus promoting osteogenic differentiation of BMSCs.

INTRODUCTION: Osteoporosis is the most susceptible disease for people over 60. The main cause of osteoporosis is the decreased osteogenic differentiation of mesenchymal stem cells (MSCs). Here we showed that upstream stimulatory factor 2 (USF2)/microRNA-34a (miR-34a)/bone morphogenetic protein 3 (BMP3) axis regulated osteogenic differentiation of BMSCs. MATERIALS AND METHODS: USF2 and miR-34a expression were examined using qPCR. Protein levels of BMP3 and osteogenic markers expression were evaluated using both western blot and qPCR. Activity of ALP was determined by ALP assay kit. Mineralization capacity of hBMSCs was assessed using ARS. Besides, CHIP assay was employed to verify whether USF2 could bind to miR-34a promoter. Finally, RIP assay and dual-luciferase reporter assay were employed to verify whether miR-34a directly bound to BMP3. RESULTS: Our results suggested that miR-34a was upregulated during osteogenic differentiation of BMSCs, and miR-34a overexpression could enhance osteogenic differentiation of BMSCs. USF2 could positively regulate miR-34a expression by interacting with its promoter. USF2 overexpression enhanced osteogenic differentiation of BMSCs, while miR-34a inhibition reversed the effect. Besides, BMP3 was the target of miR-34a. MiR-34a overexpression enhanced osteogenic differentiation of BMSCs, which was abolished by BMP3 overexpression. CONCLUSION: Taken together, USF2 enhanced osteogenic differentiation of BMSCs via downregulating BMP3 by interacting with miR-34a promoter.

Artesunate promotes osteoblast differentiation through miR-34a/DKK1 axis.

BACKGROUND: Osteoporosis is characterised by impairment of microarchitecture and bone mass. Therapeutic strategy promoting osteoblast differentiation is considered as a promising direction for the treatment of osteoporosis. Artesunate (ART) is related to osteoporosis, but the relationship between ART and osteogenic differentiation is still unknown. METHODS: Cells proliferation were measured by MTT, ALP activity assay and Alizarin Red S staining were used to assess osteogenic differentiation of hBMSCs. Western blotting and qRT-PCR were applied for measuring expression of protein and mRNA, respectively. The relationship between miR-34a and Dickkopf-1 (DKK1) was detected by dual luciferase reporter assay. RESULTS: The expression of osteoblasts differentiation related proteins (Runx2, OCN, and OPN) were significantly increased by ART. And ART accelerates the osteoblasts differentiation of hBMSCs through promoting Wnt signaling pathway by DKK1 inhibition. Significant higher expression of miR-34a and lower expression of DKK1 could be induced by ART. We firstly proved that miR-34a could bind DKK1 specifically. CONCLUSION: ART could promote osteoblast differentiation through miR-34a/DKK1/Wnt pathway. Therefore, our findings may provide a new thought for the treatment of osteoporosis by ART through osteoblast differentiation promotion.

[Clinical applications of sternoclavicular hook plate for the treatment of sternoclavicular joint dislocation].

OBJECTIVE: To observe the clinical therapeutic effects of sternoclavicular hook plate for the treatment of sternoclavicular joint dislocation. METHODS: From June 2010 to June 2012, 7 patients with sternoclavicular joint dislocation were treated with sternoclavicular hook plate fixation. Among the 7 patients, 5 patients were male and 2 patients were female, and the average age was 42.3 years, ranging from 38 to 54 years. The course of the disease ranged from 1 to 4 weeks. All the patients had trauma history. The clinical manifestations included: obvious swelling and pain of sternoclavicular joint, restricted shoulder joint activity. The sternoclavicular joint dislocation was proved by preoperative X-ray and CT. The postoperative curative effect was evaluated according to Rockwood scoring method. RESULTS: According to Rockwood scoring method, the excellent results obtained in 6 cases, good in 1. There were no complications such as internal fixation loosening or broken, second dislocation, pain in the sternoclavicular joint, and deformity. The function of shoulder joint was good, and the limb activity was free and no pain appeared. CONCLUSION: The sternoclavicular hook plate for the treatment of sternoclavicular joint dislocation has follow advantages: simple procedure, stable fixation, definite therapeutic effects.

[A short-term follow-up results of lumbar disc herniation by Coflex].

OBJECTIVE: To evaluate the short term effectiveness of lumbar disc herniation by Coflex. METHODS: From December 2007 to June 2008, 31 patients (16 males and 15 females) were treated by Coflex. The average age was 51.4 years (range, 33 - 70 years). The average period of follow-up was 10 months. To evaluate the short term effectiveness of lumbar disc herniation by Coflex by JOA, VAS, the conventional radiography and oswestry disability index (ODI). RESULTS: The average JOA score increased from 9.1 +/- 1.1 preoperatively to 26.4 +/- 1.7 at 6 month postoperatively. ODI decreased from 24.7 +/- 4.8 preoperatively to averaged 4.5 +/- 1.1 at 6 months postoperatively. The VAS score decreased from 7.9 +/- 0.8 to 3.0 +/- 0.9. The clinical symptoms after operation were improved significantly. There were statistically significant differences between the preoperative and postoperative HD (height of dorso- intervertebral discs), DS(distance across the two adjacent spinous processes), DI (distance of intervertebral foramina). The average HD increased from (7.9 +/- 1.1) mm preoperatively to (10.8 +/- 1.3) mm after operation. The average DS increased from (28.3 +/- 2.4) mm preoperatively to (36.4 +/- 1.7) mm postoperatively. The average DI changed from (18.8 +/- 1.0) mm preoperatively to (21.6 +/- 1.7) mm postoperatively. Complications occurred in 3 patients (9.6%). One case complained of persistent low back pain. One case showed opposite lower limb pain in 3 weeks after operation, and was cured after appropriate treatment. One case had the loosening of Coflex in 6 months after surgery, but did not appear related clinical symptoms. CONCLUSION: Coflex for lumbar disc herniation can increase the HD and DI significantly, and it has positive meaning for keeping height of lumbar vertebral space and treating the nerve root symptom of lumbar disc herniation.