Artesunate inhibits osteoclastogenesis through the miR-503/RANK axis.

Osteoporosis is a metabolic bone disease that is characterized by decreased bone density and strength due to excessive loss of bone protein and mineral content, which can be induced by increased osteoclast activity. Developing agents targeting osteoclast activation is considered to be the most effective method to reverse bone destruction and alleviate the pain caused by osteoporosis. MTT assay was conducted to detect the cell viability after artesunate treatment of RAW264.7 cells. TRACP staining and pit formation assays were performed to examine the TRACP-positive cells and pit-forming activity of osteoclasts. qRT-PCR and Western blot analysis were performed to assess the mRNA and protein expression levels of the osteoclastogenesis-related genes NFATc1, TRAP, and cathepsin k. The protein levels of RANK, p-Akt, p-p38, and p-ERK were examined by Western blotting. Luciferase reporter assay was conducted to determine whether miR-503 targeted RANK directly. Artesunate inhibited TRACP-positive cells and the pit-forming activity of osteoclasts. However, artesunate increased the expression of miR-503. Artesunate suppressed osteoclastogenesis-related gene expression and RANKL-induced activation of MAPKs and the AKT pathway. In addition, miR-503 inhibited RANK expression by directly targeting RANK during osteoclast differentiation. Artesunate inhibited osteoclastogenesis and osteoclast functions in vitro by regulating the miR-503/RANK axis and suppressing the MAPK and AKT pathways, which resulted in decreased expression of osteoclastogenesis-related markers.

[Case-control study on modified Weaver-Dunn surgery combined with clavical hook-plate internal fixation for the treatment of Tossy type III acromioclavicular dislocation].

OBJECTIVE: To compare therapeutic effects of clavicular hook-plate fixation and modified Weaver-Dunn surgery combined with clavicular hook-plate fixation in treating Tossy type III acromioclavicular joint dislocation. METHODS: Forty-one patients with Tossy type III acromioclavicular dislocation treated by operation were retrospectively analysis from January 2012 to January 2014. The patients were divided into clavicular hook-plate fixation group (group A) and modified Weaver-Dunn surgery combined with clavicular hook-plate fixation (group B) according to surgical procedures. In group A, there were 15 males and 6 females aged from 17 to 51 years old with an average of (31.60 ± 12.58) years old, preoperative Constant-Murley score was 40.25 ± 9.80, and treated with clavicular hook-plate fixation. In group B, there were 13 males and 7 females aged from 18 to 48 years old with an average of (29.40 ± 11.27) years old, preoperative Constant-Murley score was 41.45 ± 8.81, and treated with modified Weaver-Dunn surgery combined with clavicular hook-plate fixation. Operative time, blood loss, imaging changes before and after operation, postoperative complications were compared; Constant-Murley score at 3, 6 and 12 months after operation were evaluated. RESULTS: In group A, operative time was 40.50 ± 24.36) min, blood loss was (75.30 ± 30.36) ml; In group B, operative time was (60.10 ± 23.55) min, blood loss was (100.70 ± 40.12) ml. Twenty-one patients in group A were followed-up from 12 to 18 months with an average of (14.8 ± 3.1) months; 20 patients in group B were followed-up from 12 to 14 months with an average of (13.6 ± 1.5) months. There were no significant differences in operative time, blood loss and follow-up time between two groups. Complications were in six patients of group A and 3 patients of group B, and there were no significant meaning between two groups. At 6 months after operation, Constant-Murley score in group A was 88.85 ± 4.23, 92.15 ± 3.82 in group B; and had significant meaning between two groups (t = -2.56, P = 0.022 < 0.05). While there were no differences in Constant-Murley score in other times. CONCLUSION: Both of clavicular hook-plate fixation and modified Weaver-Dunn surgery combined with clavicular hook-plate fixation are effective operative methods for the treatment of Tossy type III acromioclavicular dislocation. Clavicular hook-plate fixation has advantage of less trauma, while modified Weaver-Dunn surgery combined with clavicular hook-plate fixation could reconstruct coracoclavicular ligament more stronger, clavicular hook plate could take out earlier, also improve shoulder joint function earlier.