Purpose: Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a common disease after long-term or high-dose glucocorticoid use. The pathogenesis of GIONFH is still controversial, and abnormal bone metabolism caused by glucocorticoids may be one of the important factors. Exosomes, owing to their positive effect on bone repair, show promising therapeutic effects on bone-related diseases. In this study, we hypothesised that exosomes reduce osteocyte apoptosis in rat GIONFH via the miR-21-PTEN-AKT signalling pathway.Methods: To evaluate the effects of exosomes in GIONFH, a dexamethasone-treated or exosome-treated in vitro cell model and a methylprednisolone-treated in vivo rat model were set up. In vitro, a CCK-8 assay and 5-ethynyl-2′-deoxyuridine staining were performed to evaluate the proliferation of osteocytes. Further, a terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, annexin V-fluorescein isothiocyanate-propidium iodide staining, and western blotting were conducted to evaluate the apoptosis of osteocytes. In vivo, we used micro-computed tomography and histological and immunohistochemical analyses to assess the effects of exosomes. Moreover, the mechanism of exosome action on osteocyte apoptosis through the miR-21-PTEN-AKT pathway was investigated by high-throughput RNA sequencing, fluorescence in situ hybridisation, luciferase reporter assays, and western blotting.Results: High-throughput RNA sequencing results showed that the AKT signalling pathway was up-regulated in the exosome group. Quantitative PCR and western blotting confirmed that the relative expression of genes in the AKT pathway was up-regulated. Western blotting revealed that AKT activated by exosomes inhibited osteocyte apoptosis. RNA fluorescence in situ hybridisation and luciferase reporter assays were performed to confirm the interaction between miR-21 and PTEN. According to the experiment in vivo, exosomes prevented GIONFH in a rat model as evidenced by micro-computed tomography scanning and histological and immunohistochemical analyses.Conclusions: Exosomes are effective at inhibiting osteocyte apoptosis (in MLO-Y4 cells) and at preventing rat GIONFH. These beneficial effects are mediated by the miR-21-PTEN-AKT signalling pathway.

Osteoarthritis (OA) has become recognized as a low-grade inflammatory state. Inflammatory infiltration of the synovium by macrophages, T cells, B cells, and other immune cells is often observed in OA patients and plays a key role in the pathogenesis of OA. Hence, orchestrating the local inflammatory microenvironment and tissue regeneration microenvironment is important for the treatment of OA. Mesenchymal stem cells (MSCs) offer the potential for cartilage regeneration owing to their effective immunomodulatory properties and anti-inflammatory abilities. The paracrine effect, mediated by MSC-derived extracellular vehicles (EVs), has recently been suggested as a mechanism for their therapeutic properties. In this review, we summarize the interactions between MSCs or MSC-derived EVs and OA-related immune cells and discuss their therapeutic effects in OA. Additionally, we discuss the potential of MSC-derived EVs as a novel cell-free therapy approach for the clinical treatment of OA.

Sarcopenia is a common disease in older people due to aging, and it can also occur in midlife because of diseases including cancer. Sarcopenia, characterized by rapid loss of muscle mass and accelerated loss of function, can lead to adverse outcomes such as frailty, falls, and even mortality. The development of pharmacological and therapeutic approaches to treat sarcopenia remains challenging. The growth status and quantity of myoblasts are the key factors directly affecting muscle formation. Therefore, enhancing the function of myoblasts is crucial for the treatment of sarcopenia. In our study, we introduced an insulin-like growth factor-I (IGF-1) mimicking supramolecular nanofibers/hydrogel formed by Nap-FFGSSSR that effectively promoted proliferation and significantly reduced dexamethasone-induced apoptosis of myoblasts, assisted myoblasts to differentiate into myotubes, and prevented the fibrosis of muscle tissue and the deposition of collagen, ultimately achieving outstanding effects in the treatment of sarcopenia. The RNA-sequencing results revealed that our nanofibers possessed similar bioactivity to the growth factor IGF-1, which increased the phosphorylation of Akt by activating the insulin signaling pathway. We prepared novel supramolecular nanomaterials to reverse glucocorticoid-induced myoblast dysfunction, which was promising for the treatment of muscular atrophy. In addition, we envisioned the generation of biofunctional nanomaterials by molecular self-assembly for the treatment of chronic diseases in middle-aged and older people.

Repair of articular cartilage defects is a challenging aspect of clinical treatment. Kartogenin (KGN), a small molecular compound, can induce the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) into chondrocytes. Here, we constructed a scaffold based on chondrocyte extracellular matrix (CECM) and poly(lactic-co-glycolic acid) (PLGA) microspheres (MP), which can slowly release KGN, thus enhancing its efficiency. Cell adhesion, live/dead staining, and CCK-8 results indicated that the PLGA(KGN)/CECM scaffold exhibited good biocompatibility. Histological staining and quantitative analysis demonstrated the ability of the PLGA(KGN)/CECM composite scaffold to promote the differentiation of BMSCs. Macroscopic observations, histological tests, and specific marker analysis showed that the regenerated tissues possessed characteristics similar to those of normal hyaline cartilage in a rabbit model. Use of the PLGA(KGN)/CECM scaffold may mimic the regenerative microenvironment, thereby promoting chondrogenic differentiation of BMSCs in vitro and in vivo. Therefore, this innovative composite scaffold may represent a promising approach for acellular cartilage tissue engineering.

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