State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No.14(th), Third section, Renmin south road, Chengdu, China; Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, No.14(th), Third section, Renmin south road, Chengdu, China.
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No.14(th), Third section, Renmin south road, Chengdu, China.
Cell Signal. 2021 Mar;79:109873. doi: 10.1016/j.cellsig.2020.109873. Epub 2020 Dec 5.
Generally, impaired bones heal by bone repair and bone regeneration. These two processes are necessary during the healing period of dental implant. Vasculature plays a crucial role in bone healing because bones are highly vascularized tissue. Osteogenesis and angiogenesis are highly coupled processes and can be regulated by Hippo-YAP signaling pathway. Recent studies have demonstrated Hippo-YAP pathway may be regulated by alpha calcitonin gene-related peptide. However, the regulatory effects of αCGRP-YAP pathway on angiogenesis and osteogenesis during bone healing around implants remain unclear. Four groups of mice were established: KO Group: αCGRP mice; KO + αCGRP group: αCGRP mice with αCGRP overexpressing lentiviral transfection; KO + YAP group: αCGRP mice with YAP overexpressing lentiviral transfection; WT group: wildtype mice. After 14 or 28 days, animals were sacrificed and tested. Results showed αCGRP deficiency hampered osteogenesis and angiogenesis. In addition, the impaired bone healing can be rescued by overexpressing αCGRP and YAP in αCGRP mice. In-vivo results indicate αCGRP-YAP pathway promotes angiogenesis and osteogenesis in bone healing, especially at the early stage. Taken together, present study demonstrated αCGRP up-regulate the expression of YAP, and down-stream genes to promote the osteogenesis and angiogenesis around the implants.
一般来说,受损的骨骼通过骨修复和骨再生来愈合。这两个过程是牙种植体愈合期所必需的。脉管系统在骨愈合中起着至关重要的作用,因为骨骼是高度血管化的组织。成骨和血管生成是高度偶联的过程,可以通过 Hippo-YAP 信号通路来调节。最近的研究表明,Hippo-YAP 通路可能受到α降钙素基因相关肽的调节。然而,αCGRP-YAP 通路在种植体周围骨愈合过程中对血管生成和骨生成的调节作用尚不清楚。建立了四组小鼠:KO 组:αCGRP 小鼠;KO+αCGRP 组:αCGRP 小鼠过表达 αCGRP 慢病毒转染;KO+YAP 组:αCGRP 小鼠过表达 YAP 慢病毒转染;WT 组:野生型小鼠。14 或 28 天后,处死动物并进行测试。结果表明,αCGRP 缺乏会阻碍成骨和血管生成。此外,在 αCGRP 小鼠中过表达 αCGRP 和 YAP 可以挽救受损的骨愈合。体内结果表明,αCGRP-YAP 通路在骨愈合过程中促进血管生成和骨生成,尤其是在早期阶段。总之,本研究表明 αCGRP 上调 YAP 的表达,并下调下游基因,以促进种植体周围的成骨和血管生成。