{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:37:23Z","timestamp":1760146643447,"version":"build-2065373602"},"reference-count":46,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,24]],"date-time":"2024-11-24T00:00:00Z","timestamp":1732406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82100972","2021M703689","2020A1515111032"],"award-info":[{"award-number":["82100972","2021M703689","2020A1515111032"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["82100972","2021M703689","2020A1515111032"],"award-info":[{"award-number":["82100972","2021M703689","2020A1515111032"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["82100972","2021M703689","2020A1515111032"],"award-info":[{"award-number":["82100972","2021M703689","2020A1515111032"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Genetic abnormalities of the parathyroid hormone 1 receptor (PTH1R) lead to profound craniomaxillofacial bone and dentition defects on account of inappropriate tissue metabolism and cellular differentiation. The coordinated activity of differentiation and viability in bone cells is indispensable for bone metabolism. Recent research demonstrates mesenchymal progenitors are responsive to PTH1R signaling for osteogenic differentiation, whereas the effect of PTH1R on cellular survival remains incompletely understood. Here, we report that mice with deletion of PTH1R in Prx1-positive mesenchymal cells (Prx1Cre;PTH1Rfl\/fl) exhibit decreased alveolar bone mass due in part to apoptotic response activation. The exploration of oral bone-derived mesenchymal stem cells (OMSCs) with PTH1R deficiency suggests PTH1R signaling modulates OMSCs\u2019 apoptosis by interfering mitochondrial function and morphology. The underlying molecular mechanisms are studied by transcriptome sequencing analysis, finding that inositol trisphosphate receptor-3 (IP3R-3), an endoplasmic reticulum calcium channel protein, serves as a modulator of pro-apoptosis in OMSCs. Furthermore, we find PTH1R and its downstream protein kinase A (PKA) pathway dampen IP3R-3\u2019s expression. Of note, OMSCs with IP3R-3 overexpression recapitulate the PTH1R-deletion phenotypes, while IP3R-3 silence rescues mitochondrial dysfunction. Altogether, our study uncovers the anti-apoptotic function of PTH1R signaling in OMSCs and proves that excess apoptosis partly contributes to a weakening potential of osteogenic differentiation and aberrant mandibular development.<\/jats:p>","DOI":"10.3390\/ijms252312607","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T03:59:01Z","timestamp":1732507141000},"page":"12607","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PTH1R Suppressed Apoptosis of Mesenchymal Progenitors in Mandibular Growth"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9972-7343","authenticated-orcid":false,"given":"Chen","family":"Cui","sequence":"first","affiliation":[{"name":"Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China"},{"name":"Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5115-3351","authenticated-orcid":false,"given":"Chuang","family":"Lu","sequence":"additional","affiliation":[{"name":"Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China"},{"name":"Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanling","family":"Cai","sequence":"additional","affiliation":[{"name":"Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China"},{"name":"Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhua","family":"Xiong","sequence":"additional","affiliation":[{"name":"Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China"},{"name":"Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7237-0885","authenticated-orcid":false,"given":"Yihong","family":"Duan","sequence":"additional","affiliation":[{"name":"Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China"},{"name":"Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaiwen","family":"Lan","sequence":"additional","affiliation":[{"name":"Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China"},{"name":"Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7511-9872","authenticated-orcid":false,"given":"Yi","family":"Fan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuedong","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5749-2910","authenticated-orcid":false,"given":"Xi","family":"Wei","sequence":"additional","affiliation":[{"name":"Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China"},{"name":"Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/cdd.2016.165","article-title":"Loss of menin in osteoblast lineage affects osteocyte-osteoclast crosstalk causing osteoporosis","volume":"24","author":"Liu","year":"2017","journal-title":"Cell Death Differ."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1177\/0022034516668321","article-title":"Roles of Chondrocytes in Endochondral Bone Formation and Fracture Repair","volume":"96","author":"Hinton","year":"2017","journal-title":"J. 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