Received: 5 June 2018 | Accepted: 2 August 2018 DOI: 10.1002/jcp.27311 ORIGINAL RESEARCH ARTICLE Overexpression of αCGRP promotes osteogenesis of periodontal ligament cells by regulation of YAP signaling Lin Xiang 1,2 | Xinyuan Zhang 1,2 | Hui Yu 1 | Bin Wang 1,2 | Zhihui Lin 1,2 | Ping Gong 1,2 1 State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China 2 Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China Correspondence Ping Gong, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14th, 3rd Section, Renmin South Road, Chengdu 610041, China. Email: dentistgong@hotmail.com Funding information Youth Science Foundation of West China Hospital of Stomatology of Sichuan University, Grant/Award Number: 2016‐11; Fundamental Research Funds for the Central Universities, Grant/Award Numbers: 2017SCU12056, 2018SCUH0006; National Natural Science Foundation of China, Grant/Award Number: 81701007; China Postdoctoral Science Foundation Grant, Grant/Award Number: 2018M631091; Sichuan Science and Technology Program, Grant/Award Number: 2018RZ0087 Abstract Human periodontal ligament cells (hPDLCs) are considered as an ideal cell type for periodontal tissue engineering as hPDLCs own mesenchymal stem cell‐like proper- ties. Additionally, it is suggested that α‐calcitonin gene‐related peptide (αCGRP) plays a pivotal role in the pathogenesis of periodontitis. However, the specific role of αCGRP on the regulation of alveolar bone regeneration which is essential for treatment of periodontitis remains unclear. In this study, lentiviral αCGRP expression vector was first transfected into hPDLCs. αCGRP expression and the osteogenesis‐ related gene (ALP, RUNX2, OCN, and BSP) expressions were detected. The results showed that expressions of osteogenic phenotypes were upregulated in αCGRP‐ transfected hPDLCs combined with an increased expression of Yes‐associated protein (YAP), which is the key downstream effectors of Hippo pathway. Our observations suggest that αCGRP‐mediated hPDLCs’ osteogenesis might relate with the activity of YAP signaling. These observations may reflect intrinsic functions of αCGRP in hPDLCs’ osteogenesis and its promising role in the treatment of bone deficiency in periodontal regeneration. KEYWORDS α‐calcitonin gene‐related peptide, human periodontal ligament cells, osteogenesis, periodontal regeneration, yes‐associated protein 1 | INTRODUCTION Periodontitis is a chronic inflammation that extends deep into the tissues and causes loss of supporting connective tissue as well as alveolar bone, and, ultimately, leads to the loosening and loss of teeth (Lamster & Pagan, 2017; Pihlstrom, Michalowicz, & Johnson, 2005). It is widely accepted that there is a close correlation between periodontitis and systemic diseases. Epidemiological and case–control studies have shown that periodontitis is associated with cardiovascular disease, prediabetes, and metabolic syndrome (Tonetti et al., 2007; Watanabe & Cho, 2014). Severe periodontitis is the sixth most prevalent disease in the world and the main cause of disability‐adjusted life‐years among oral conditions (Marcenes et al., 2013). Thus, the treatment of periodontitis has been a focus of attention and study, among which, functional regeneration of periodontal apparatus especially the alveolar bone has been one of the most important aims of research in current periodontal regenerative therapy and preprosthetic, preimplantology surgery (Orciani et al., 2009; Wang et al., 2010). Although various approaches have been developed to regenerate destroyed periodontal tissues including guided tissue regeneration, bone grafting, and the use of enamel matrix derivative, complete and predictable periodontal regeneration has rarely achieved (F. M. Chen & Jin, 2010; Esposito, Grusovin, Papanikolaou, Coulthard, & Worthington, 2009; Su et al., 2015). J Cell Physiol. 2018;1–9. wileyonlinelibrary.com/journal/jcp © 2018 Wiley Periodicals, Inc. | 1