Background: Stabilization and increased activity of hypoxia-inducible factor 1-α (HIF-1α) can directly increase cancellous bone formation and play an essential role in bone modeling and remodeling. However, whether an increased HIF-1α expression in adipose-derived stem cells (ADSCs) increases osteogenic capacity and promotes bone regeneration is not known.Results: In this study, ADSCs transfected with small interfering RNA and HIF-1α overexpression plasmid were established to investigate the proliferation, migration, adhesion, and osteogenic capacity of ADSCs and the angiogenic ability of human umbilical vein endothelial cells (HUVECs). Overexpression of HIF-1α could promote the biological functions of ADSCs, and the angiogenic ability of HUVECs. Western blotting showed that the protein levels of osteogenesis-related factors were increased when HIF-1α was overexpressed. Furthermore, the influence of upregulation of HIF-1α in ADSC sheets on osseointegration was evaluated using a Sprague–Dawley (SD) rats implant model, in which the bone mass and osteoid mineralization speed were evaluated by radiological and histological analysis. The overexpression of HIF-1α in ADSCs enhanced bone remodeling and osseointegration around titanium implants. However, transfecting the small interfering RNA (siRNA) of HIF-1α in ADSCs attenuated their osteogenic and angiogenic capacity. Finally, it was confirmed in vitro that HIF-1α promotes osteogenic differentiation and the biological functions in ADSCs via the VEGF/AKT/mTOR pathway.Conclusions: This study demonstrates that HIF-1α has a critical ability to promote osteogenic differentiation in ADSCs by coupling osteogenesis and angiogenesis via the VEGF/AKT/mTOR signaling pathway, which in turn increases osteointegration and bone formation around titanium implants.Graphical

Peri-implantitis is characterized by inflammatory cell infiltration and hyperactivation of the osteoclasts surrounding dental implants which can result in bone resorption and ultimately implant failure. Therefore, coordinating the activity of inflammatory response and bone-resorbing osteoclasts is crucial for the prevention of peri-implantitis. Asperuloside (ASP), an iridoid glycoside, has significant anti-inflammatory activities, suggesting the great potential in attenuating peri-implantitis bone resorption. A ligature-induced peri-implantitis model in the maxilla of rats was established, and the effects of ASP on preventing peri-implantitis were evaluated after four weeks of ligation using micro-CT and histological staining. RT-PCR, western blotting, tartrate-resistant acid phosphatase (TRAP), and immunofluorescent staining were conducted on osteoclasts to confirm the mechanisms of ASP on osteoclastogenesis. The results show that ASP could lead to attenuation of alveolar bone resorption in peri-implantitis by inhibiting osteoclast formation and decreasing pro-inflammatory cytokine levels in vivo. Furthermore, ASP could inhibit osteoclastogenesis by downregulating expression levels of transcription factors nuclear factor of activated T-cell (NFATc1) via restraining the activations of nuclear factor kappa beta (NF-κB) and the phosphorylation of extracellular signal-related kinase 1/2 (ERK1/2). In conclusion, ASP could significantly attenuate bone resorption in peri-implantitis via inhibition of osteoclastogenesis by suppressing NF-κB and ERK1/2 signaling pathways activations.

Graphical Inhibition of PTEN simultaneously improved the anti-inflammatory effect and osteogenic capacity of TADSCs, and ultimately promoted peri-implant bone formation in T2DM rats.

Melanin is the natural physiological defense for skin, but excessive melanin production can result in conditions like hyperpigmentation and melasma. In addition to UV light, visible light, especially blue light, has been recognized as an extra factor contributing to cutaneous hyperpigmentation and premature photoaging. However, there are currently no effective protective agents against blue light. Within this research, we obtained polydopamine nanoparticles (PDA NPs) and cuttlefish ink nanoparticles (CINPs), which are inspired by endogenous melanin. Our research confirmed that PDA NPs and CINPs shared similar structural and functional properties with natural melanin. Otherwise, these nanoparticles not only exhibited excellent photostability and broad-spectrum ultraviolet–visible light absorption capabilities but also possessed superb biocompatibility and antioxidant properties. Experiments conducted in vitro and in vivo verified that PDA NPs and CINPs could effectively hold back melanin production and alleviate pigmentation. Furthermore, we found that the underlying mechanism by which PDA NPs and CINPs reduced melanin formation was through inhibition of the FZD2-TYR-melanin signaling pathway. Taken together, our findings not only demonstrate that PDA NPs and CINPs are powerful anti-blue light agents but also provide an in-depth mechanism of these nanoparticles in the inhibition of pigment formation.

Periodontal disease is widely recognised as a chronic infectious-inflammatory disorder, leading to the destruction of alveolar bone. Osteoclasts and their progenitors have been demonstrated to play pivotal roles in the process of periodontitis-induced bone damage. The mechanisms that govern the differentiation of osteoclasts in the context of periodontitis remain to be elucidated. In this study, we assessed the expression of CD226 on osteoclasts and their progenitors, as well as the function of CD226 in experimental periodontitis mice. Periodontitis was induced in C57BL/6 wild-type and CD226 knockout (CD226-KO) mice. Micro-CT was used to analyse bone loss. Haematoxylin–eosin (HE) or tartrate-resistant acid phosphatase (TRAP) staining was conducted to examine osteoclast differentiation. Flow cytometric analysis and quantitative real-time PCR (qRT-PCR) were used to identify the expression of CD226 and related molecules. The expression of CD226 on osteoclasts was found to decrease gradually during the process of osteoclastogenesis. In addition, the study revealed that the knockout of CD226 inhibited osteoclast differentiation in vitro. Furthermore, the knockout of CD226 has been demonstrated to attenuate inflammatory responses and alleviate bone damage in a murine periodontitis model. The present study suggests that CD226 plays an important role in regulating the function and differentiation of osteoclasts and their progenitors. The targeting of CD226 has the potential to be developed as a potent therapy for bone loss caused by periodontitis.