Osteocytes are the main sensitive cells in bone remodeling due to their potent functional cell processes from the mineralized bone matrix to the bone surface and the bone marrow. Neighboring osteocytes communicate with each other by these cell processes to achieve molecular exchange through gap junction channels. Platelet-derived growth factor-AA (PDGF-AA) has been reported to enhance bone tissue remodeling by promoting cell proliferation, migration, and autocrine secretion in osteoid cell linage. However, the effect of PDGF-AA on intercellular communication between osteocytes is still unclear. In the present study, we elucidated that PDGF-AA could enhance the formation of dendritic processes of osteocytes and the gap junctional intercellular communication by promoting the expression of connexin43 (Cx43). This modulation process was mainly dependent on the activation of phosphorylation of Akt protein by phosphatidylinositol 3-kinase (PI3K)/Akt (also known as protein kinase B, PKB) signaling. Inhibition of PI3K/Akt signaling decreased the Cx43 expression induced by PDGF-AA. These results establish a bridge between PDGF-AA and cell–cell communication in osteocytes, which could help us understand the molecular exchange between bone cells and fracture healing.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial membrane inflammation, osteophyte formation, and subchondral bone sclerosis. Pathological changes in cartilage and subchondral bone are the main processes in OA. In recent decades, many studies have demonstrated that activin-like kinase 3 (ALK3), a bone morphogenetic protein receptor, is essential for cartilage formation, osteogenesis, and postnatal skeletal development. Although the role of bone morphogenetic protein (BMP) signalling in articular cartilage and bone has been extensively studied, many new discoveries have been made in recent years around ALK3 targets in articular cartilage, subchondral bone, and the interaction between the two, broadening the original knowledge of the relationship between ALK3 and OA. In this review, we focus on the roles of ALK3 in OA, including cartilage and subchondral bone and related cells. It may be helpful to seek more efficient drugs or treatments for OA based on ALK3 signalling in future.

Mineralized tissues, such as teeth and bones, pose significant challenges for repair due to their hardness, low permeability, and limited blood flow compared to soft tissues. Bone morphogenetic proteins (BMPs) have been identified as playing a crucial role in mineralized tissue formation and repair. However, the application of large amounts of exogenous BMPs may cause side effects such as inflammation. Therefore, it is necessary to identify a more precise molecular target downstream of the ligands. Activin receptor-like kinase 3 (ALK3), a key transmembrane receptor, serves as a vital gateway for the transmission of BMP signals, triggering cellular responses. Recent research has yielded new insights into the regulatory roles of ALK3 in mineralized tissues. Experimental knockout or mutation of ALK3 has been shown to result in skeletal dysmorphisms and failure of tooth formation, eruption, and orthodontic tooth movement. This review summarizes the roles of ALK3 in mineralized tissue regulation and elucidates how ALK3-mediated signaling influences the physiology and pathology of teeth and bones. Additionally, this review provides a reference for recommended basic research and potential future treatment strategies for the repair and regeneration of mineralized tissues.

Background: Growing pieces of evidence demonstrate a close relationship between bone regeneration disorders of diabetic patients and NOD-like receptor thermal protein domain associated protein 3（NLRP3）. Drugs targeting NLRP3 in the treatment of diabetic bone disorders have been heatedly discussed in recent years, and new R&D ideas should be explored. Objective: This review analyzes molecular mechanisms of how hyperglycemia activates NLRP3 and leads to bone disorders in diabetic patients. Also, this review focuses on the research of drugs targeting NLRP3 inflammasome in the treatment of diabetic bone disorders, and eventually points out the ideas for new drug development. Results: In diabetic patients, hyperglycemia ultimately increases the expression of NLRP3 inflammasome which cleaves pro-IL-1β into mature IL-1β by caspase-1, leading to impaired bone formation. Drugs targeting NLRP3 inflammasome are divided into two categories. Indirect-acting drugs for NLRP3 inflammasomes include dipeptidyl peptidase-4 inhibitors, lipoxygen A4, epigallocatechin gallate, and vitamin D3. Direct-acting drugs include Glyburide, Dioscin, and Pristimerin. Conclusion: The presented studies indicate that hyperglycemia is the initiating factor for NLRP3-induced bone disorders in diabetic patients. The main drug targets are the molecules relevant to the assembly and activation of NLRP3 inflammasome. These data may provide a theoretical basis for the further development of drugs targeting NLRP3 inflammasome in the treatment of diabetic bone disorders.