Abstract
The social demand for dental implantation is growing at a rapid rate, while dentists are faced with the dilemma of implantation failures associated with unfavorable osseointegration. Clinical-friendly osteogenesis, angiogenesis and osteoimmunology around dental implants play a pivotal role in a desirable osseointegration and it’s increasingly appreciated that Hippo-YAP signaling pathway is implicated in those biological processes both in vitro and in vivo in a variety of study. In this article we review the multiple effects of Hippo-YAP signaling in osseointegration of dental implants by regulating osteogenesis, angiogenesis and osteoimmunology in peri-implant tissue, as well as highlight prospective future directions of relevant investigation.
Highlights
With the increasing social burden of growing elderly population, some age-implicated diseases are changing people’s demand for medical services including tooth loss
The regulation effects of lysophosphatidic acid (LPA) on bone metabolism are mainly mediated by LPA1, LPA3, and LPA4 (Liu et al, 2010; Chen et al, 2019; Wu et al, 2019; Alioli et al, 2020); LPA4 and LPA6 play a facilitating role in developmental angiogenesis and LPA1 and LPA3 are found to mediate LPA/PKD-1-CD36 axis regulating proangiogenic and proarteriogenic reprogramming and de novo arteriogenesis (Ren et al, 2016; Dong et al, 2017; Yasuda et al, 2019); it is worth noticing that LPA contributes to the formation of macrophages from monocytes in both mice and humans (Ray and Rai, 2017) and promotes LPA1 and LPA3 mediated conversion to foam cells (Chen et al, 2017)
The investigations around LPA suggest the potential role of LPA on osteogenesis, angiogenesis and osteoimmunology which may facilitate osseointegration procedure of implants, while its specific mechanism remains to be further clarified
Summary
With the increasing social burden of growing elderly population, some age-implicated diseases are changing people’s demand for medical services including tooth loss. By regulating expression of key genes, Hippo-YAP signaling pathway plays a versatile and significant regulatory role in organ development and regeneration in mammal, indicating their potential impacts on osseointegration induced by osteogenesis, angiogenesis and osteoimmunology. Song et al (2020) revealed the mechanism of YAP aggravating M1 phenotype in Kupffer cells that LPS-stimulated YAP upregulated expression of the classic proinflammatory cytokines including IL-6, TNF-α, and MCP-1 by binding to their promoter regions through association with its transcriptional factor TEADs. Besides macrophages, there are other immune cells should be involved in this discussion, since they dominate early inflammatory response in the primary stage of osseointegration. Further study may uncover the role of Hippo-YAP in early peri-implant inflammatory response
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