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Wound healing can be divided into different phases, and timely initiation and cessation of these stages is key to successful wound healing; otherwise, scar tissue forms in the wounded area. Connexins (Cxs) were confirmed to influence scar formation, and Cx43, an indispensable member of the Cx family, was shown to be involved in this process. Our study investigated the regulatory role of Cx43 in scar formation and the possible cell signalling pathways. We established oral mucosa and skin wound healing models in C57BL/6J mice. RT‐PCR, western blotting, immunohistochemistry and immunofluorescence were used to examine the expression of ECM components and key proteins in cell signalling pathways (TGF‐β1, Smad2/3, Cx43, Erk1/2 MMP‐1 and collagen III). After injury, buccal mucosa wounds healed with no scar, whereas skin wounds healed with an evident scar. Nevertheless, TGF‐β1 expression gradually increased by the 5th day after injury; Cx43 expression showed a similar response, with a progressive increase in the skin and a peak on day 14. In contrast, TGF‐β1 and Cx43 expression in the oral mucosa remained low. The high level of TGF‐β1 increased p‐Smad2/3 levels and then induced Cx43, whereas increased expression of Cx43 antagonised the phosphorylation of Erk1/2, a protein downstream of Cx43, which affected MMP‐1 synthesis. MMP‐1 deficiency led to collagen III accumulation and facilitated scar formation. We demonstrated that TGF‐β1‐induced Cx43 promotes scar formation via the Erk/MMP‐1/collagen III pathway. [ABSTRACT FROM AUTHOR]

Objectives: The present study was designed to investigate the effects of microRNA‐21 (miR‐21) on orthodontic tooth movement. Methods: The orthodontic tooth movement model was established in C57BL/6 and miR‐21−/− mice with or without implantation of activated T cells. Histological and histomorphometrical analyses were performed by hematoxylin–eosin staining. Tartrate‐resistant acid phosphate staining was used to analyze the osteoclast numbers during tooth movement. Enzyme‐linked immunosorbent assay, reverse transcription polymerase chain reaction, and immunohistochemistry analysis were used to examine the expression of RANKL and OPG. Results: In miR‐21−/− mice, the distance of tooth movement was retarded, the osteoclast number was decreased, and serum RANKL expression was strongly reduced. MiR‐21 promoted the secretion of RANKL from activated T cells. Furthermore, activated T cells could partially rescue the decreased orthodontic tooth movement distance in miR‐21−/− mice. MiR‐21 was shown to promote orthodontic tooth movement by modulating the RANKL/OPG balance in T cells. Conclusions: The impact of miR‐21 on tooth movement was better elucidated, furthering our understanding of its role and clinical applications in orthodontics. [ABSTRACT FROM AUTHOR]

PERK (EIF2AK3) is an ER-resident eIF2α kinase required for memory flexibility and metabotropic glutamate receptor-dependent long-term depression, processes known to be dependent on new protein synthesis. Here we investigated PERK’s role in working memory, a cognitive ability that is independent of new protein synthesis, but instead is dependent on cellular Ca2+ dynamics. We found that working memory is impaired in forebrain-specific Perk knockout and pharmacologically PERK-inhibited mice. Moreover, inhibition of PERK in wild-type mice mimics the fear extinction impairment observed in forebrain-specific Perk knockout mice. Our findings reveal a novel role of PERK in cognitive functions and suggest that PERK regulates both Ca2+ -dependent working memory and protein synthesis-dependent memory flexibility. [ABSTRACT FROM AUTHOR]