{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T07:30:13Z","timestamp":1774942213376,"version":"3.50.1"},"reference-count":44,"publisher":"Portland Press Ltd.","issue":"8","license":[{"start":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T00:00:00Z","timestamp":1628121600000},"content-version":"vor","delay-in-days":4,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,8,27]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Periodontitis is a series of inflammatory processes caused by bacterial infection. Parathyroid hormone (PTH) plays a critical role in bone remodeling. The present study aimed to investigate the influences of PTH on human bone marrow mesenchymal stem cells (HBMSCs) pretreated with lipopolysaccharide (LPS). The proliferative ability was measured using cell counting kit-8 (CCK-8) and flow cytometry. The optimal concentrations of PTH and LPS were determined using alkaline phosphatase (ALP) activity assay, ALP staining, and Alizarin Red staining. Osteogenic differentiation was further assessed by quantitative reverse-transcription polymerase chain reaction (RT-qPCR), Western blot analysis, and immunofluorescence staining. PTH had no effects on the proliferation of HBMSCs. Also, 100 ng\/ml LPS significantly inhibited HBMSC osteogenesis, while 10\u22129 mol\/l PTH was considered as the optimal concentration to reverse the adverse effects. Mechanistically, c-Jun N-terminal kinase (JNK) phosphorylation was activated by PTH in LPS-induced HBMSCs. SP600125, a selective inhibitor targeting JNK mitogen-activated protein kinase (MAPK) signaling, weakened the effects of PTH. Taken together, the findings revealed the role and mechanism of PTH and JNK pathway in promoting the osteogenic differentiation of LPS-induced HBMSCs, which offered an alternative for treating periodontal diseases.<\/jats:p>","DOI":"10.1042\/bsr20210420","type":"journal-article","created":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T08:30:33Z","timestamp":1628152233000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Parathyroid hormone promotes the osteogenesis of lipopolysaccharide-induced human bone marrow mesenchymal stem cells through the JNK MAPK pathway"],"prefix":"10.1042","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1520-8272","authenticated-orcid":false,"given":"Ziyue","family":"Qin","sequence":"first","affiliation":[{"name":"Department of Periodontology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China"},{"name":"Jiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu","family":"Hua","sequence":"additional","affiliation":[{"name":"Jiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China"},{"name":"Department of Temporomandibular Joint, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huifen","family":"Chen","sequence":"additional","affiliation":[{"name":"Jiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China"},{"name":"Department of Endodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuo","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China"},{"name":"Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haoran","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China"},{"name":"Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiamin","family":"Xu","sequence":"additional","affiliation":[{"name":"Jiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China"},{"name":"Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5500-3351","authenticated-orcid":false,"given":"Yuli","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China"},{"name":"Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Periodontology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China"},{"name":"Jiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weina","family":"Zhou","sequence":"additional","affiliation":[{"name":"Jiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China"},{"name":"Department of Temporomandibular Joint, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2021,8,20]]},"reference":[{"key":"2021111620511887800_B1","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1016\/S0140-6736(05)67728-8","article-title":"Periodontal diseases","volume":"366","author":"Pihlstrom","year":"2005","journal-title":"Lancet North Am. Ed."},{"key":"2021111620511887800_B2","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1177\/154405910708600310","article-title":"Functional TLRs and NODs in human gingival fibroblasts","volume":"86","author":"Uehara","year":"2007","journal-title":"J. Dent. Res."},{"key":"2021111620511887800_B3","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/nri1004","article-title":"Innate immune sensing and its roots: the story of endotoxin","volume":"3","author":"Beutler","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"2021111620511887800_B4","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1002\/(SICI)1097-4644(199702)64:2<278::AID-JCB11>3.0.CO;2-F","article-title":"Growth kinetics, self-renewal, and the osteogenic potential of purified human mesenchymal stem cells during extensive subcultivation and following cryopreservation","volume":"64","author":"Bruder","year":"1997","journal-title":"J. Cell. Biochem."},{"key":"2021111620511887800_B5","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1089\/hum.2010.173","article-title":"The regulation of differentiation in mesenchymal stem cells","volume":"21","author":"Augello","year":"2010","journal-title":"Hum. Gene Ther."},{"key":"2021111620511887800_B6","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1359\/jbmr.1997.12.6.989","article-title":"The effect of aging on bone formation in porous hydroxyapatite: biochemical and histological analysis","volume":"12","author":"Inoue","year":"1997","journal-title":"J. Bone Miner. Res."},{"key":"2021111620511887800_B7","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1046\/j.1365-3083.2003.01176.x","article-title":"Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex","volume":"57","author":"Le Blanc","year":"2003","journal-title":"Scand. J. Immunol."},{"key":"2021111620511887800_B8","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1634\/stemcells.2005-0403","article-title":"Accumulated chromosomal instability in murine bone marrow mesenchymal stem cells leads to malignant transformation","volume":"24","author":"Miura","year":"2006","journal-title":"Stem Cells"},{"key":"2021111620511887800_B9","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.bbrc.2007.06.023","article-title":"Bacterial lipopolysaccharide induces osteoclast formation in RAW 264.7 macrophage cells","volume":"360","author":"Islam","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021111620511887800_B10","doi-asserted-by":"crossref","first-page":"3330","DOI":"10.1016\/j.molimm.2008.04.022","article-title":"Lipopolysaccharides (LPS) induce the differentiation of human monocytes to osteoclasts in a tumour necrosis factor (TNF) alpha-dependent manner: a link between infection and pathological bone resorption","volume":"45","author":"Mormann","year":"2008","journal-title":"Mol. Immunol."},{"key":"2021111620511887800_B11","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.bone.2013.02.023","article-title":"PTH prevents the adverse effects of focal radiation on bone architecture in young rats","volume":"55","author":"Chandra","year":"2013","journal-title":"Bone"},{"key":"2021111620511887800_B12","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.cmet.2015.09.012","article-title":"IL-17A is increased in humans with primary hyperparathyroidism and mediates PTH-induced bone loss in mice","volume":"22","author":"Li","year":"2015","journal-title":"Cell Metab."},{"key":"2021111620511887800_B13","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1002\/jbmr.2714","article-title":"PTH promotes bone anabolism by stimulating aerobic glycolysis via IGF signaling","volume":"30","author":"Esen","year":"2015","journal-title":"J. Bone Miner. Res."},{"key":"2021111620511887800_B14","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1172\/JCI6610","article-title":"Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone","volume":"104","author":"Jilka","year":"1999","journal-title":"J. Clin. Invest."},{"key":"2021111620511887800_B15","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1002\/jcb.21816","article-title":"Teriparatide (1-34 human PTH) regulation of osterix during fracture repair","volume":"105","author":"Kaback","year":"2008","journal-title":"J. Cell. Biochem."},{"key":"2021111620511887800_B16","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.bbrc.2009.01.167","article-title":"Effects of continuous and pulsatile PTH treatments on rat bone marrow stromal cells","volume":"380","author":"Yang","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021111620511887800_B17","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1210\/en.2002-220863","article-title":"Activation of p38 mitogen-activated protein kinase is required for osteoblast differentiation","volume":"144","author":"Hu","year":"2003","journal-title":"Endocrinology"},{"key":"2021111620511887800_B18","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1101\/gad.13.11.1464","article-title":"The Drosophila p38 MAPK pathway is required during oogenesis for egg asymmetric development","volume":"13","author":"Suzanne","year":"1999","journal-title":"Genes Dev."},{"key":"2021111620511887800_B19","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.jep.2015.11.020","article-title":"Xanthii fructus inhibits inflammatory responses in LPS-stimulated RAW 264.7 macrophages through suppressing NF-kappaB and JNK\/p38 MAPK","volume":"176","author":"Yeom","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"2021111620511887800_B20","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.bone.2005.10.027","article-title":"Skeletal site-specific characterization of orofacial and iliac crest human bone marrow stromal cells in same individuals","volume":"38","author":"Akintoye","year":"2006","journal-title":"Bone"},{"key":"2021111620511887800_B21","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.lfs.2009.04.010","article-title":"The 15-deoxy-Delta12,14-prostaglandin J2 inhibits LPS-stimulated AKT and NF-kappaB activation and suppresses interleukin-6 in osteoblast-like cells MC3T3E-1","volume":"85","author":"Jung","year":"2009","journal-title":"Life Sci."},{"key":"2021111620511887800_B22","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1002\/stem.663","article-title":"Inhibition of osteogenic differentiation of human adipose-derived stromal cells by retinoblastoma binding protein 2 repression of RUNX2-activated transcription","volume":"29","author":"Ge","year":"2011","journal-title":"Stem Cells"},{"key":"2021111620511887800_B23","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.joen.2014.01.042","article-title":"Mineral trioxide aggregate promotes the odonto\/osteogenic differentiation and dentinogenesis of stem cells from apical papilla via nuclear factor kappa B signaling pathway","volume":"40","author":"Yan","year":"2014","journal-title":"J. Endod."},{"key":"2021111620511887800_B24","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1002\/jcp.29034","article-title":"Parathyroid hormone enhances the osteo\/odontogenic differentiation of dental pulp stem cells via ERK and P38 MAPK pathways","volume":"235","author":"Ge","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"2021111620511887800_B25","doi-asserted-by":"crossref","first-page":"592","DOI":"10.3389\/fphar.2020.00592","article-title":"The transcription factor Foxc1 promotes osteogenesis by directly regulating Runx2 in response of intermittent parathyroid hormone (1-34) treatment","volume":"11","author":"Ouyang","year":"2020","journal-title":"Front. Pharmacol."},{"key":"2021111620511887800_B26","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1007\/s10753-013-9778-9","article-title":"Lipopolysaccharide (LPS) induces the apoptosis and inhibits osteoblast differentiation through JNK pathway in MC3T3-E1 cells","volume":"37","author":"Guo","year":"2014","journal-title":"Inflammation"},{"key":"2021111620511887800_B27","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.3892\/ijmm.2015.2130","article-title":"SP600125 reduces lipopolysaccharide-induced apoptosis and restores the early-stage differentiation of osteoblasts inhibited by LPS through the MAPK pathway in MC3T3-E1 cells","volume":"35","author":"Guo","year":"2015","journal-title":"Int. J. Mol. Med."},{"key":"2021111620511887800_B28","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.yexcr.2016.11.003","article-title":"Role of human amnion-derived mesenchymal stem cells in promoting osteogenic differentiation by influencing p38 MAPK signaling in lipopolysaccharide -induced human bone marrow mesenchymal stem cells","volume":"350","author":"Wang","year":"2017","journal-title":"Exp. Cell. Res."},{"key":"2021111620511887800_B29","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/s41419-017-0231-0","article-title":"Epigenetic inhibition of Wnt pathway suppresses osteogenic differentiation of BMSCs during osteoporosis","volume":"9","author":"Jing","year":"2018","journal-title":"Cell Death Dis."},{"key":"2021111620511887800_B30","doi-asserted-by":"crossref","first-page":"38491","DOI":"10.1038\/srep38491","article-title":"miR-27a attenuates adipogenesis and promotes osteogenesis in steroid-induced rat BMSCs by targeting PPARgamma and GREM1","volume":"6","author":"Gu","year":"2016","journal-title":"Sci. Rep."},{"key":"2021111620511887800_B31","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1002\/jcp.22201","article-title":"Porphyromonas gingivalis lipopolysaccharide inhibits the osteoblastic differentiation of preosteoblasts by activating Notch1 signaling","volume":"225","author":"Xing","year":"2010","journal-title":"J. Cell. Physiol."},{"key":"2021111620511887800_B32","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1002\/jor.21028","article-title":"The roles of TNFR1 in lipopolysaccharide-induced bone loss: dual effects of TNFR1 on bone metabolism via osteoclastogenesis and osteoblast survival","volume":"28","author":"Ochi","year":"2010","journal-title":"J. Orthop. Res."},{"key":"2021111620511887800_B33","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1002\/jor.1100090504","article-title":"Mesenchymal stem cells","volume":"9","author":"Caplan","year":"1991","journal-title":"J. Orthop. Res."},{"key":"2021111620511887800_B34","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1111\/j.1474-9726.2011.00735.x","article-title":"Age-related decline in osteoblastogenesis and 1alpha-hydroxylase\/CYP27B1 in human mesenchymal stem cells: stimulation by parathyroid hormone","volume":"10","author":"Geng","year":"2011","journal-title":"Aging Cell"},{"key":"2021111620511887800_B35","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1002\/jbmr.1663","article-title":"Parathyroid hormone induces differentiation of mesenchymal stromal\/stem cells by enhancing bone morphogenetic protein signaling","volume":"27","author":"Yu","year":"2012","journal-title":"J. Bone Miner. Res."},{"key":"2021111620511887800_B36","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1111\/j.1474-9726.2010.00616.x","article-title":"Decreased oxidative stress and greater bone anabolism in the aged, when compared to the young, murine skeleton with parathyroid hormone administration","volume":"9","author":"Jilka","year":"2010","journal-title":"Aging Cell"},{"key":"2021111620511887800_B37","first-page":"1","article-title":"Periodontal biology: stem cells, Bmp2 Gene, transcriptional enhancers, and use of sclerostin antibody and Pth for treatment of periodontal disease and bone loss","volume":"3","author":"Harris","year":"2017","journal-title":"Cell Stem Cells Regen. Med."},{"key":"2021111620511887800_B38","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1007\/s00223-017-0259-2","article-title":"Bone alkaline phosphatase and tartrate-resistant acid phosphatase: potential co-regulators of bone mineralization","volume":"101","author":"Halling Linder","year":"2017","journal-title":"Calcif. Tissue Int."},{"key":"2021111620511887800_B39","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.colsurfb.2014.08.005","article-title":"Collagen type-I leads to in vivo matrix mineralization and secondary stabilization of Mg-Zr-Ca alloy implants","volume":"122","author":"Mushahary","year":"2014","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"2021111620511887800_B40","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1016\/j.biocel.2008.03.020","article-title":"Osteopontin and skeletal muscle myoblasts: association with muscle regeneration and regulation of myoblast function in vitro","volume":"40","author":"Uaesoontrachoon","year":"2008","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"2021111620511887800_B41","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1359\/jbmr.060109","article-title":"BMP signaling is required for RUNX2-dependent induction of the osteoblast phenotype","volume":"21","author":"Phimphilai","year":"2006","journal-title":"J. Bone Miner. Res."},{"key":"2021111620511887800_B42","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1242\/jcs.02758","article-title":"Glucocorticoid-induced osteogenesis is negatively regulated by Runx2\/Cbfa1 serine phosphorylation","volume":"119","author":"Phillips","year":"2006","journal-title":"J. Cell Sci."},{"key":"2021111620511887800_B43","doi-asserted-by":"crossref","first-page":"10491","DOI":"10.3390\/ijms160510491","article-title":"Regulative effect of Mir-205 on osteogenic differentiation of bone mesenchymal stem cells (BMSCs): possible role of SATB2\/Runx2 and ERK\/MAPK pathway","volume":"16","author":"Hu","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"2021111620511887800_B44","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.lfs.2015.03.017","article-title":"Extracellular regulated protein kinases play a key role via bone morphogenetic protein 4 in high phosphate-induced endothelial cell apoptosis","volume":"131","author":"Qin","year":"2015","journal-title":"Life Sci."}],"container-title":["Bioscience Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20210420\/919440\/bsr-2021-0420.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20210420\/919440\/bsr-2021-0420.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T23:01:43Z","timestamp":1699311703000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/bioscirep\/article\/41\/8\/BSR20210420\/229448\/Parathyroid-hormone-promotes-the-osteogenesis-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8]]},"references-count":44,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2021,8,27]]}},"URL":"https:\/\/doi.org\/10.1042\/bsr20210420","relation":{},"ISSN":["0144-8463","1573-4935"],"issn-type":[{"value":"0144-8463","type":"print"},{"value":"1573-4935","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,8]]},"published":{"date-parts":[[2021,8]]},"article-number":"BSR20210420"}}