The clinical need for effective bone regeneration therapy remains in huge demands. However, the current “gold standard” treatments of autologous and allogeneic bone grafts may result in various complications. Furthermore, safety considerations of biomaterials and cell-based treatment require further clarification. Therefore, developing new therapies with stronger osteogenic potential and a lower incidence of complications is worthwhile. Recently, exosomes, small vesicles of endocytic origin, have attracted attention in bone regeneration field. The vesicles travel between cells and deliver functional cargoes, such as proteins and RNAs, thereby regulating targeted cells differentiation, commitment, function, and proliferation. Much evidence has demonstrated the important roles of exosomes in osteogenesis both in vitro and in vivo. In this review, we summarize the properties, origins and biogenesis of exosomes, and the recent reports using exosomes to regulate osteogenesis and promote bone regeneration.

The aim of this study was to assess the effect of naringenin on osteoclastogenesis and titanium particle-induced osteolysis. Osteolysis from wear-induced particles and aseptic loosening are the most frequent late complications of total joint arthroplasty leading to revision of the prosthesis. Osteolysis during aseptic loosening is most likely due to increased bone resorption by osteoclasts. Through in vitro studies, we demonstrated that naringenin, a naturally occurring flavanone in grapefruit and tomatoes, exerts potent inhibitory effects on the ligand of the receptor activator of nuclear factor-κB (RANKL)-induced osteoclastogenesis and revealed that the mechanism of action of naringenin, which inhibited osteoclastogenesis by suppression of the p38 signaling pathway. Through in vivo studies, we proved that naringenin attenuated titanium particle-induced osteolysis in a mouse calvarial model. In general, we demonstrated that naringenin inhibited osteoclastogenesis via suppression of p38 signaling in vitro and attenuated titanium particle-induced osteolysis in vivo. This study also suggested that naringenin has significant potential for the treatment of osteolysis-related diseases caused by excessive osteoclast formation and activity.

Periodontitis is a common chronic inflammatory disease, which leads to alveolar bone resorption. Healthy and functional alveolar bone, which can support the teeth and enable their movement, is very important for orthodontic treatment. Myricetin inhibited osteoclastogenesis by suppressing the expression of some genes, signaling pathways, and cytokines. This study aimed to investigate the effects of myricetin on alveolar bone loss in an ovariectomized (OVX) mouse model of periodontitis as well as in vitro osteoclast formation and bone resorption. Twenty-four healthy eight-week-old C57BL/J6 female mice were assigned randomly to four groups: phosphate-buffered saline (PBS) control (sham) OVX + ligature + PBS (vehicle), and OVX + ligature + low or high (2 or 5 mg∙kg⁻¹∙day⁻¹, respectively) doses of myricetin. Myricetin or PBS was injected intraperitoneally (i.p.) every other day for 30 days. The maxillae were collected and subjected to further examination, including micro-computed tomography (micro-CT), hematoxylin and eosin (H&E) staining, and tartrate-resistant acid phosphatase (TRAP) staining; a resorption pit assay was also performed in vitro to evaluate the effects of myricetin on receptor activator of nuclear factor κ-B ligand (RANKL)-induced osteoclastogenesis. Myricetin, at both high and low doses, prevented alveolar bone resorption and increased alveolar crest height in the mouse model and inhibited osteoclast formation and bone resorption in vitro. However, myricetin was more effective at high dose than at low dose. Our study demonstrated that myricetin had a positive effect on alveolar bone resorption in an OVX mouse model of periodontitis and, therefore, may be a potential agent for the treatment of periodontitis and osteoporosis.

Insulin resistance (IR) is defined as impaired insulin function, reduced glucose uptake and increased glucose production, which can result in type II diabetes, metabolic syndrome and even bone metabolic disorders. A possible reason for the increasing incidence of IR is population aging. Adipose tissue (AT) is an important endocrine organ that serves a crucial role in whole‑body energy homeostasis. AT can be divided into white AT (WAT), beige AT and brown AT (BAT). Several mechanisms have been previously associated with age‑dependent IR in WAT. However, BAT, a metabolically active tissue, controls the levels of plasma glucose and triglyceride metabolism. Therefore, the present review aimed to summarize the mechanisms of age‑dependent IR induced by AT and to determine the role of WAT browning in achieving positive therapeutic outcomes in age‑dependent IR.

Osteoarthritis (OA) is a chronic, whole-joint disorder marked by progressive cartilage degradation, subchondral bone remodeling, synovial inflammation, and capsular fibrosis, affecting over 500 million individuals worldwide. Current pharmacotherapies are mainly palliative, with no approved disease-modifying osteoarthritis drugs (DMOADs). Intra-articular (IA) injection provides direct joint access but is hampered by rapid drug clearance and short residence times. Injectable liposome–microsphere (iLMP) systems have recently emerged as integrative delivery platforms that synergistically combine the high loading capacity, targeting versatility, and stimuli-responsiveness of liposomes with the sustained release, lubrication, mechanical support, and protective shielding of hydrogel microspheres. This “nano-in-micro” hierarchical architecture enables prolonged joint retention, spatiotemporally controlled drug release, active cell/tissue targeting, and even gene editing, thereby shifting OA management from symptom alleviation toward true disease modification. In this review, we systematically examine the rational design of iLMPs, covering liposomal composition and functionalization, microsphere fabrication technologies (microfluidics, electrospraying, 3D bioprinting, emulsification), and assembly strategies (embedding, anchoring, adsorption, and matrix hybridization). We then detail their physicochemical determinants—size, surface charge, rheology, and degradation kinetics—and discuss the multifaceted therapeutic mechanisms, including sustained pharmacokinetic modulation, boundary lubrication, active/passive targeting, enzyme/ROS/pH-responsive release, nucleic acid delivery, and exosome-hybrid biofunctionalization. Finally, we critically analyze current translational barriers (scale-up, long-term stability, safety, and cost) and outline future directions toward intelligent, personalized, and combination regimens. With continued advances in biomaterials, microengineering, and precision medicine, iLMPs are poised to become a cornerstone of next-generation OA therapy.