Mechanical stress plays a critical role in cartilage development and homoeostasis. Chondrocytes are surrounded by a narrow pericellular matrix (PCM), which absorbs dynamic and static forces and transmits them to the chondrocyte surface. Recent studies have demonstrated that molecular components, including perlecan, collagen and hyaluronan, provide distinct physical properties for the PCM and maintain the essential microenvironment of chondrocytes. These physical signals are sensed by receptors and molecules located in the cell membrane, such as Ca²⁺ channels, the primary cilium and integrins, and a series of downstream molecular pathways are involved in mechanotransduction in cartilage. All mechanoreceptors convert outside signals into chemical and biological signals, which then regulate transcription in chondrocytes in response to mechanical stresses. This review highlights recent progress and focuses on the function of the PCM and cell surface molecules in chondrocyte mechanotransduction. Emerging understanding of the cellular and molecular mechanisms that regulate mechanotransduction will provide new insights into osteoarthritis pathogenesis and precision strategies that could be used in its treatment.

Sirtuins are a family of nicotinamide adenine dinucleotide (NAD)⁺-dependent histone deacetylases, comprising seven members SIRT1-SIRT7. Sirtuins have been extensively studied in regulating ageing and age-related diseases. Sirtuins are also pivotal modulators in oxidative stress and inflammation, as they can regulate the expression and activation of downstream transcriptional factors (such as Forkhead box protein O3 (FOXO3a), nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-κB)) as well as antioxidant enzymes, through epigenetic modification and post-translational modification. Most importantly, studies have shown that aberrant sirtuins are involved in the pathogenesis of infectious and inflammatory oral diseases, and oral cancer. In this review, we provide a comprehensive overview of the regulatory patterns of sirtuins at multiple levels, and the essential roles of sirtuins in regulating inflammation, oxidative stress, and bone metabolism. We summarize the involvement of sirtuins in several oral diseases such as periodontitis, apical periodontitis, pulpitis, oral candidiasis, oral herpesvirus infections, dental fluorosis, and oral cancer. At last, we discuss the potential utilization of sirtuins as therapeutic targets in oral diseases.

A common feature of many acute and chronic oral diseases is microbial-induced inflammation. Innate immune responses are the first line of defense against pathogenic microorganisms and are initiated by pattern recognition receptors (PRRs) that specifically recognize pathogen-associated molecular patterns and danger-associated molecular patterns. The activation of certain PRRs can lead to the assembly of macromolecular oligomers termed inflammasomes, which are responsible for pro-inflammatory cytokine maturation and secretion and thus activate host inflammatory responses. About 10 years ago, the absent in melanoma 2 (AIM2) was independently discovered by four research groups, and among the “canonical” inflammasomes [including AIM2, NLR family pyrin domain (NLRP)1, NLRP3, NLR family apoptosis inhibitory protein (NAIP)/NLR family, caspase activation and recruitment domain (CARD) containing (NLRC)4, and pyrin], AIM2 so far is the only one that simultaneously acts as a cytosolic DNA sensor due to its DNA-binding ability. Undoubtedly, such a double-faceted role gives AIM2 greater mission and more potential in the mediation of innate immune responses. Therefore, AIM2 has garnered much attention from the broad scientific community during its first 10 years of discovery (2009–2019). How the AIM2 inflammasome is related to oral diseases has aroused debate over the past few years and is under active investigation. AIM2 inflammasome may potentially be a key link between oral diseases and innate immunity. In this review, we highlight the current knowledge of the AIM2 inflammasome and its critical role in the pathogenesis of various oral diseases, which might offer future possibilities for disease prevention and targeted therapy utilizing this continued understanding.

Orthopedic and dental implantations under bacterial infection microenvironment face significant challenges in achieving high-quality bone-implant integration. Designing implant coatings that incorporate both immune defense and anti-inflammation is difficult in conventional single-functional coatings. We introduce a multifunctional nanointerface using a zinc finger-inspired peptide-metal-phenolic nanocoating, designed to enhance implant osseointegration under such conditions. Abaloparatide (ABL), a second-generation anabolic drug for treating osteoporosis, can be integrated into the design of a zinc-phenolic network constructed on the implant surface (ABL@ZnTA). Importantly, the phenolic-coordinated Zn²⁺ ions in ABL@ZnTA can act as zinc finger motif to co-stabilize the configuration of ABL through multiple molecular interactions, enabling high bioactivity, high loading capacity (1.36 times), and long-term release (>7 days) of ABL. Our results showed that ABL@ZnTA can modulate macrophage polarization from the pro-inflammatory M1 towards the anti-inflammatory M2 phenotype, promoting immune osteogenesis with increased OCN, ALP, and SOD 1 expression. Furthermore, the ABL@ZnTA significantly reduces inflammatory fibrous tissue encapsulation and enhances the long-term stability of the implants, indicated by enhanced binding strength (6 times) and functional connectivity (1.5-3 times) in the rat bone defect model infected by S. aureus. Overall, our research offers a nano-enabled synergistic strategy that balances infection defense and osteogenesis promotion in orthopedic and dental implantations.

Endothelial dysfunction is a critical factor during the initiation of atherosclerosis. Berberine has a beneficial effect on endothelial function; however, the underlying mechanisms remain unclear. In this study, we investigated the effects of berberine on lipopolysaccharide‐ (LPS‐) induced apoptosis in human umbilical vein endothelial cells (HUVECs) and the molecular mechanisms mediating the effect. The effects of berberine on LPS‐induced cell apoptosis and viability were measured with 5‐ethynyl‐2′‐deoxyuridine staining, flow cytometry, and Cell Counting Kit‐8 assays. The expression and/or activation of proapoptotic and antiapoptotic proteins or signaling pathways, including caspase‐3, poly(ADP‐ribose) polymerase, myeloid cell leukemia‐1 (MCL‐1), p38 mitogen‐activated protein kinase, C‐Jun N‐terminal kinase (JNK), and extracellular signal‐regulated kinase, were determined with western blotting. The malondialdehyde levels, superoxide dismutase (SOD) activity, and production of proinflammatory cytokines were measured with enzyme‐linked immunosorbent assays. The results demonstrated that berberine pretreatment protected HUVECs from LPS‐induced apoptosis, attenuated LPS‐induced injury, inhibited LPS‐induced JNK phosphorylation, increased MCL‐1 expression and SOD activity, and decreased proinflammatory cytokine production. The effects of berberine on LPS‐treated HUVECs were prevented by SP600125, a JNK‐specific inhibitor. Thus, berberine might be a potential candidate in the treatment of endothelial cell injury‐related vascular diseases.