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Background The imbalance of osteogenic/adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is closely related to steroid-induced avascular necrosis of the femoral head (SANFH). We aimed to investigate the epigenetic mechanism of intramedullary fat accumulation and continuous osteonecrosis after glucocorticoid (GC) withdrawal in SANFH. Methods An SANFH model was established in SD rats, which received an intermittent high GC dose for the first 4 weeks followed by an additional 4 weeks without GC. We explored the synergistic effects and mechanisms of C/EBPα and PPARγ on the differentiation of BMSCs by lentivirus-mediated gene knockdown and overexpression assays. A chromatin immunoprecipitation assay was performed to identify epigenetic modification sites on PPARγ in vivo and in vitro. Results In the SANFH model, intramedullary fat was significantly increased, and the transcription factors C/EBPα and PPARγ were upregulated simultaneously in the femoral head. In vitro, C/EBPα promoted adipogenic differentiation of BMSCs by targeting the PPARγ signalling pathway, while overexpression of C/EBPα significantly impaired osteogenic differentiation. Further studies demonstrated that histone H3K27 acetylation of PPARγ played an important role in the epigenetic mechanism underlying SANFH. C/EBPα upregulates the histone H3K27 acetylation level in the PPARγ promoter region by inhibiting HDAC1. Additionally, inhibiting the histone acetylation level of PPARγ effectively prevented adipogenic differentiation, thus slowing the progression of SANFH. Conclusions Our results demonstrate the molecular mechanism by which C/EBPα regulates PPARγ expression by acetylating histones and revealed the epigenetic phenomenon in SANFH for the first time. Graphical abstract

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Background: Skin avulsion injuries caused by high-energy traffic and machinery accidents are important topics in the field of repair and reconstruction. The injury generates a skin flap with uncertain vascular basis resulting in ischemic necrosis of the distal portion of the flap. Yet there is lack of reliable way for estimating the extent of blood supply in damaged tissue, which has limited the possibility of prompt surgical intervention. Recent studies have confirmed that photoacoustic microscopy imaging has a wide range of applications in the biomedical field owing to its good performance in angiography. Methods: In our study, we successfully surgically induced skin avulsion injury on mice hindlimbs. Then, we used this novel approach to image skin microcirculation and predict skin necrosis with impaired blood supply after injury in live mice. Results and Conclusion:All skin tissues in the avulsed hindlimb flap group show different levels of necrosis at the end of the observation period. The "dark zone" with impaired microcirculation in PAM images, which continuously extends over time, was seen as a prediction of necrosis of skin tissue and at 60 min after surgery was similar to the area of clinical necrosis on postoperative day 7. All these indicate that photoacoustic microscopy imaging is a feasible, precise, high-resolution, non-invasive technique for early prediction of necrosis in skin avulsion injury, providing a promising tool for surgeons to manage the injury.

Bioinspired strontium magnesium phosphate cements for bone tissue engineering were prepared using a new, facile, environmentally friendly and high yielding (98.5%) precursor method. The bioinspired SMPCs have uniform particle distributions, excellent mechanical strengths and high biocompatibilities. The in vitro responses of bone marrow stromal cells to the SMPCs, including viability, osteogenic differentiation and alkaline phosphatase activity, were evaluated. The results show that the SMPC containing 0.5 mol of strontium (referred to as SMPC-2) has a higher degradation rate and biological activity than magnesium phosphate cements and the other SMPCs. In addition, the synergistic effect of strontium and magnesium ion release from SMPC-2 creates a conducive environment for cell proliferation, mineralized calcium deposition and new bone formation. These observations demonstrate the feasibility of using the new precursor method to generate SMPCs and the utility of these biologically compatible and highly effective cements for bone tissue engineering.