Background: Osteosarcoma is the most common primary bone malignancy in children and adolescents, and the pathogenesis of this cancer remains unclear. Therefore, the discovery of new biomarkers for the diagnosis, prognosis, and treatment of osteosarcoma remains an important but unmet clinical need. Method: Quantitative real-time PCR was carried out to examine the expression of miR-23a. Methylation-specific PCR was performed to evaluate the DNA methylation status of the miR-23a promoter. Cell proliferation, migration, and invasion were examined by cell counting assays, wound healing assays, and cell invasion assays, respectively. Western blot analysis and luciferase reporter assays were performed to identify miR-23 target genes. Nude mice were used to investigate the function of miR-23a in vivo. Results: The expression of miR-23a was decreased in osteosarcoma cells and tissues compared to normal controls. The promoter region of the miR-23a gene was hypermethylated in osteosarcoma cells, and demethylase treatment increased the expression of miR-23a. The ectopic expression of miR-23a led to retarded proliferation, migration, and invasion of osteosarcoma cells, whereas the depletion of miR-23a resulted in the opposite effects. MiR-23a suppressed the transcription of RUNX2 and CXCL12 by binding to the 3' UTRs of these mRNAs. The cellular function of miR-23a is RUNX2/CXCL12-dependent, and the overexpression of RUNX2 or CXCL12 rescued the impaired cell growth, migration, and invasion induced by miR-23a. Nude mouse experiments indicated that miR-23a may inhibit the proliferation of osteosarcoma cells in vivo. Conclusion: We identified miR-23a as a tumor suppressor in osteosarcoma. Our data clarify the mechanism of osteosarcoma progression and demonstrated the potential for exploiting miR-23a as a diagnostic marker for osteosarcoma.

In situ tissue engineering is a powerful strategy for the treatment of bone defects. It could overcome the limitations of traditional bone tissue engineering, which typically involves extensive cell expansion steps, low cell survival rates upon transplantation, and a risk of immuno-rejection. Here, a porous scaffold polycaprolactone (PCL)/decellularized small intestine submucosa (SIS) was fabricated via cryogenic free-form extrusion, followed by surface modification with aptamer and PlGF-2 123-144 *-fused BMP2 (pBMP2). The two bioactive molecules were delivered sequentially. The aptamer Apt19s, which exhibited binding affinity to bone marrow-derived mesenchymal stem cells (BMSCs), was quickly released, facilitating the mobilization and recruitment of host BMSCs. BMP2 fused with a PlGF-2 123-144 peptide, which showed “super-affinity” to the ECM matrix, was released in a slow and sustained manner, inducing BMSC osteogenic differentiation. In vitro results showed that the sequential release of PCL/SIS-pBMP2-Apt19s promoted cell migration, proliferation, alkaline phosphatase activity, and mRNA expression of osteogenesis-related genes. The in vivo results demonstrated that the sequential release system of PCL/SIS-pBMP2-Apt19s evidently increased bone formation in rat calvarial critical-sized defects compared to the sequential release system of PCL/SIS-BMP2-Apt19s. Thus, the novel delivery system shows potential as an ideal alternative for achieving cell-free scaffold-based bone regeneration in situ .

Gluteal muscle contracture (GMC), a debilitating disease, exists all over the globe but it is much more prevalent in China. Patients typically present with abduction and external rotation of the hip and are unable to bring both the knees together while squatting. Multiple etiologies have been postulated, the commonest being repeated intramuscular injection into the buttocks. The disease is diagnosed primarily by clinical features but radiological features are necessary for the exclusion of other pathological conditions. Non-operative treatment with physiotherapy can be tried before surgery is considered but it usually fails. Different surgical techniques have been described and claimed to have a better outcome of one over another but controversy still exists. Based on published literatures, the clinical outcome is exceptionally good in all established methods of surgery. However, endoscopic surgery is superior to conventional open surgery in terms of cosmetic outcome with fewer complications. Nevertheless, its use has been limited by lack of adequate knowledge, instrumentations, and some inherent limitations. Above all, post-operative rehabilitation plays a key role in better outcome, which however should be started gradually.