Glucocorticoid-induced osteonecrosis of the femoral head (ONFH) is a refractory disease. The treatment options for ONFH, especially nonsurgical ones, merit further investigation. To evaluate the combinatorial therapeutic effects of platelet-rich plasma clot releasate (PRCR) and umbilical cord mesenchymal stem cells (UC-MSCs) on glucocorticoid-induced ONFH, a dexamethasone (DEX)-treated cell model and a high-dose methylprednisolone (MPS)-treated rat model were established. Cell counting kit-8 (CCK-8) assay was performed in vitro to determine the optimum dosage of PRCR for UC-MSC viability. The effects of PRCR, UC-MSCs, and PRCR + UC-MSCs on cell viability, apoptosis, migration, and differentiation capacities of DEX-treated bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cell (HUVECs) were explored via Transwell assays. Western blotting was conducted to evaluate the expression levels of RUNX2, VEGF, caspase-3, and Bcl-2 in the coculture systems. Ultrasound-guided intra-articular PRCR, UC-MSCs, and PRCR + UC-MSC injections were performed on the ONFH model rats. Microcomputed tomography, histological and immunohistochemical analyses, tartrate-resistant acid phosphatase (TRAP) staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to assess the therapeutic effects of PRCR and UC-MSCs on bone loss and necrosis induced by high-dose MPS. Results of this study revealed that the in vitro application of PRCR, UC-MSCs, and PRCR + UC-MSCs reversed the impaired proliferation and migration capacities and resisted apoptosis of BMSCs and HUVECs induced by DEX. Moreover, the PRCR and UC-MSC application significantly improved the alkaline phosphatase (ALP) and alizarin red (ALR) staining of BMSCs and tube formation capacity of HUVECs and promoted the protein expression of RUNX2 in BMSCs and VEGF in HUVECs. Similarly, in the ONFH rat model, the intra-articular injection of UC-MSCs and PRCR improved the subchondral bone mass parameters; promoted the expression of ALP, RUNX2, and VEGF; suppressed osteoclast overactivity; and resisted cell apoptosis. The combination of PRCR and UC-MSCs shows promising therapeutic effects in treating glucocorticoid-induced ONFH. The current study provides important information on intra-articular therapy, paving the way for the clinical management of ONFH in the future.

Pressure ulcer (PU) is a common type of chronic wound that is difficult to treat. Platelet-rich plasma (PRP) is rich in cytokines and growth factors, and it can be divided into two categories according to its leukocyte content: leukocyte-poor PRP (P-PRP) and leukocyte-rich PRP (L-PRP). PRP has been applied in a variety of wound treatments, due to its strong ability to promote repair. This study aims to investigate the therapeutic effects of PRP on PU and elucidate the role of leukocytes in the treatment process. Sprague-Dawley rats were used to establish PU models of ischemia-reperfusion injury by applying magnets externally. L-PRP, P-PRP and saline were injected into the dermal wounds. Wound healing analysis and sampling were performed on days 3, 7, 11 and 15 after treatment. Histological examinations, real-time PCR, immunohistochemical examinations and biomechanical assay were carried out on the wound samples. The PRP groups exhibited greater wound inflammatory response than the control group in the early stage but the response reduced rapidly as the wound healed. On days 7, 11, and 15, the PRP groups also yielded better wound healing rates and histological outcomes than the control group, with superior biomechanical properties observed on day 15. Among both PRP groups, the L-PRP group attained a higher wound healing rate than the P-PRP group on day 7, with greater significant early inflammatory responses, and more prominent angiogenesis. Therefore, PRP is proven to accelerate the healing of PU, with L-PRP being more effective in regulating inflammation and promoting angiogenesis than P-PRP.

Background Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a progressive and disabling disease caused by long-term or high-dose glucocorticoid use. Decreased osteogenesis and proliferation of bone marrow mesenchymal stem cells (BMSCs) are the main pathogenesis of GIONFH. Platelet-rich plasma (PRP) has been shown to play a promising role in bone regeneration. However, the effects of PRP on glucocorticoid-induced BMSCs inhibition remains elusive. The objective of this study was to explore whether PRP could improve the in vitro biological activities of BMSCs inhibited by high-dose glucocorticoid in vitro. Methods In this study, a dexamethasone (Dex)-induced in vitro cell model was established. The effects of PRP on proliferation, migration, cell cycle and apoptosis of rat BMSCs induced with high-dose Dex compared to BMSCCTRL, using CCK-8 assay, transwell, flow cytometry and TUNEL assay, respectively. We further performed the alkaline phosphatase (ALP) and alizarin red (ALR) staining to explore the influence of PRP on osteogenic differentiation. Western Blot was used to detect the expression of Bcl-2, Caspase-3, RUNX2 apoptosis, and osteogenic-related proteins. Results We observed increased apoptosis rate and Caspase-3 expression, and the decreased migration and osteogenic differentiation, and down-regulation of RUNX-2 and Bcl-2 expression in Dex-induced BMSCs. PRP could reverse these inhibitory effects of Dex, and enhance the BMSCs proliferation, migration, and osteogenic ability in vitro. Conclusion Our vitro study showed that PRP significantly protected BMSCs from Dex-induced apoptosis, and further promoted BMSCs proliferation, migration, and osteogenic differentiation. This study provides a scientific basis for the prevention and treatment of GIONFH with PRP. Meanwhile, it also lays the foundation for the application of PRP in other musculoskeletal diseases.

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