Bone remodeling is a strictly regulated dynamic process that cycles between bone formation and resorption, and interleukin‐17 (IL‐17) critically orchestrates the activation and differentiation of both osteoblasts and osteoclasts. Mesenchymal stem cells (MSCs) within their native environment receive biochemical stimuli from surrounding cells that influences their differentiation into bone precursors, while the roles of osteocytes in regulating the osteogenic differentiation of MSCs remain unclear. This study investigated the specific roles of IL‐17 signaling cascades and osteocyte‐specific pathways in the osteogenesis of MSCs. Using a transwell coculture (CC) system, we explored the effects of osteocytes and osteoblasts on the osteogenesis of MSCs with and without IL‐17 supplementation. A polycaprolactone (PCL) three‐dimensional (3D) culture model was used to evaluate their osteogenic potential in the presence of osteocytes and IL‐17. Notably, IL‐17 induced osteogenesis in MSCs, which could be attenuated by blocking IL‐17 receptor A. The osteogenic differentiation of MSCs promoted by IL‐17 was further enhanced by CC with osteocytes. Moreover, proinflammatory cytokines IL‐6 and IL‐1β played an important role in IL‐17‐dependent differentiation, via the phosphorylation of AKT, signal transducer and activator of transcription 3, and extracellular signal‐regulated kinase 1/2 signaling pathways in the MSC niche. The present study confirms a synergistic effect of osteocytes and IL‐17 in the production of biochemical signals to stimulate the osteogenic differentiation of MSCs, which could be further promoted in the PCL 3D‐scaffold. These findings provide important insight into the mechanisms of MSCs activation and osteogenic differentiation within the native stem cell niche, and suggest a possible role of IL‐17 in bone tissue engineering.

Interleukin (IL)-17 is crucial to osteoclast differentiation and activation. Osteocytes support osteoclast formation and are thought to orchestrate bone remodeling in response to fluid flow. The contribution of IL-17 to osteocyte-related bone resorption remains unclear. Here, we used the osteocyte-like MLO-Y4 cell line to examine the role of IL-17 and fluid flow in osteoclastogenesis. It was the first time to demonstrate that IL-17A promoted MLO-Y4 cell proliferation, enhanced expression of receptor activator of nuclear factor κ-B ligand (RANKL) and tumor necrosis factor-α (TNF-α), and induced osteoclastogenesis when MLO-Y4 cells were co-cultured with bone marrow-derived macrophage (BMM) cells. Additionally, shear stress upregulated osteoprotegerin expression in osteocytes, downregulated the effect of IL-17A on RANKL and TNF-α expression, and attenuated IL-17A-activated osteoclastic differentiation in the co-culture system of MLO-Y4 and BMM cells. Furthermore, we explored the signaling pathways that potentially mediate these effects in osteocytes, and found that the extracellular signal-regulated kinase (ERK)1/2 and signal transducer and activator of transcription (STAT3) pathways were suppressed by IL-17A but induced by fluid flow. EphA2 signaling enhances osteoclastogenesis in osteocytes, and the intercellular reversed EphA2-ephrinA2 signaling from osteocytes to BMM play an important role in IL-17A-dependent osteoclastic differentiation. EphB4 signaling inhibits osteoclastogenesis in osteocytes, and the intercellular reversed EphB4-ephrinB2 signaling from osteocytes to BMM could inhibit IL-17A-dependent osteoclastic differentiation. The current findings suggest that IL-17A as a promoter of bone resorption and fluid shear stress critically regulate bone remodeling via osteocyte-specific signaling pathways. IL-17 modulation-based approaches may be developed as a novel therapeutic strategy for enhancing bone remodeling efficiency and stability.

The cranial base plays an important role in determining how the mandible and maxilla relate to each other. This study assessed the relationship between the cranial base and jaw base in a Chinese population.

The osteogenic function of mesenchymal stem cells (MSCs) is mainly attributed to the paracrine effect of extracellular vesicles. MSC-derived exosomes are interesting candidates as biopharmaceuticals for drug delivery and for the engineering of biologically functionalized materials, and have emerged as cell-free regenerative medicine in recent years. In this study, bone marrow mesenchymal stem cell (BMSC)-derived exosomes were loaded with photothermal material layered black phosphorus (BP) modified poly(N-isopropylacrylamide) (PNIPAAm) thermosensitive hydrogels to explore their effects on bone defect repair. In vitro, it was confirmed that the local high heat of nano-BP irradiated using a near-infrared (NIR) laser could trigger the reversible cascade reaction of hydrogels, and that the mechanical contraction of hydrogels led to the controllable release of a large number of exosomes along with the release of water molecules. Furthermore, in vitro investigations demonstrated that BP hydrogels loaded with BMSC-derived exosomes had favourable biocompatibility and could promote the proliferation and osteogenic differentiation of MSCs. Experiments conducted in vivo confirmed that this system significantly promoted bone regeneration. Therefore, the results of our study indicated that the nanoplatform based on BP thermosensitive hydrogels could provide a new clinical treatment strategy for controlled release and on-demand drug delivery, while the cell-free system composed of BMSC-derived exosomes had great application potential in bone tissue repair with the synergism of BP.