{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T14:06:44Z","timestamp":1791986804344,"version":"4.4.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2016,7,14]],"date-time":"2016-07-14T00:00:00Z","timestamp":1468454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,7,14]],"date-time":"2016-07-14T00:00:00Z","timestamp":1468454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Microenvironmental conditions can interfere with the functional role and differentiation of mesenchymal stem cells (MSCs). Recent studies suggest that an inflammatory microenvironment can significantly impact the osteogenic potential of periodontal ligament stem cells (PDLSCs), but the precise effects and mechanisms involved remain unclear. Here, we show for the first time that interleukin-1<jats:italic>\u03b2<\/jats:italic>(IL-1<jats:italic>\u03b2<\/jats:italic>) has dual roles in the osteogenesis of PDLSCs at concentrations ranging from physiologically healthy levels to those found in chronic periodontitis. Low doses of IL-1<jats:italic>\u03b2<\/jats:italic>activate the BMP\/Smad signaling pathway to promote the osteogenesis of PDLSCs, but higher doses of IL-1<jats:italic>\u03b2<\/jats:italic>inhibit BMP\/Smad signaling through the activation of nuclear factor-<jats:italic>\u03ba<\/jats:italic>B (NF-<jats:italic>\u03ba<\/jats:italic>B) and mitogen-activated protein kinase (MAPK) signaling, inhibiting osteogenesis. These results demonstrate that crosstalk between NF-<jats:italic>\u03ba<\/jats:italic>B, MAPK and BMP\/Smad signaling mediates this dual effect of IL-1<jats:italic>\u03b2<\/jats:italic>on PDLSCs. We also show that the impaired osteogenesis of PDLSCs results in more inflammatory cytokines and chemokines being released, inducing the chemotaxis of macrophages, which further clarifies the role of PDLSCs in the pathogenesis of periodontitis.<\/jats:p>","DOI":"10.1038\/cddis.2016.204","type":"journal-article","created":{"date-parts":[[2016,7,14]],"date-time":"2016-07-14T13:47:37Z","timestamp":1468504057000},"page":"e2296-e2296","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":124,"title":["Double-edged-sword effect of IL-1\u03b2 on the osteogenesis of periodontal ligament stem cells via crosstalk between the NF-\u03baB, MAPK and BMP\/Smad signaling pathways"],"prefix":"10.1038","volume":"7","author":[{"given":"C-y","family":"Mao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y-g","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X-y","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T-t","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E-y","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,7,14]]},"reference":[{"key":"BFcddis2016204_CR1","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1902\/jop.2005.76.8.1406","volume":"76","author":"B Burt","year":"2005","unstructured":"Burt B . Position paper: epidemiology of periodontal diseases. J Periodontol 2005; 76: 1406\u20131419.","journal-title":"J Periodontol"},{"key":"BFcddis2016204_CR2","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1177\/0022034512458692","volume":"91","author":"PN Papapanou","year":"2012","unstructured":"Papapanou PN . The prevalence of periodontitis in the US: forget what you were told. J Dent Res 2012; 91: 907\u2013908.","journal-title":"J Dent Res"},{"key":"BFcddis2016204_CR3","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1634\/stemcells.2007-0734","volume":"26","author":"Y Liu","year":"2008","unstructured":"Liu Y, Zheng Y, Ding G, Fang D, Zhang C, Bartold PM et al. Periodontal ligament stem cell-mediated treatment for periodontitis in miniature swine. Stem Cells 2008; 26: 1065\u20131073.","journal-title":"Stem Cells"},{"key":"BFcddis2016204_CR4","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1016\/j.jdent.2009.03.001","volume":"37","author":"M Kunze","year":"2009","unstructured":"Kunze M, Huber A, Krajewski A, Lowden E, Schuhmann N, Buening H et al. Efficient gene transfer to periodontal ligament cells and human gingival fibroblasts by adeno-associated virus vectors. J Dent 2009; 37: 502\u2013508.","journal-title":"J Dent"},{"key":"BFcddis2016204_CR5","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1177\/0022034509340867","volume":"88","author":"GT Huang","year":"2009","unstructured":"Huang GT, Gronthos S, Shi S . Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine. J Dent Res 2009; 88: 792\u2013806.","journal-title":"J Dent Res"},{"key":"BFcddis2016204_CR6","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1111\/j.1600-051X.2011.01716.x","volume":"38","author":"JC Park","year":"2011","unstructured":"Park JC, Kim JM, Jung IH, Kim JC, Choi SH, Cho KS et al. Isolation and characterization of human periodontal ligament (PDL) stem cells (PDLSCs) from the inflamed PDL tissue: in vitro and in vivo evaluations. J Clin Periodontol 2011; 38: 721\u2013731.","journal-title":"J Clin Periodontol"},{"key":"BFcddis2016204_CR7","doi-asserted-by":"publisher","first-page":"5119","DOI":"10.1016\/j.bbagen.2013.07.027","volume":"1830","author":"X Kong","year":"2013","unstructured":"Kong X, Liu Y, Ye R, Zhu B, Zhu Y, Liu X et al. GSK3beta is a checkpoint for TNF-alpha-mediated impaired osteogenic differentiation of mesenchymal stem cells in inflammatory microenvironments. Biochim Biophys Acta 2013; 1830: 5119\u20135129.","journal-title":"Biochim Biophys Acta"},{"key":"BFcddis2016204_CR8","doi-asserted-by":"publisher","first-page":"2554","DOI":"10.1111\/j.1349-7006.2010.01731.x","volume":"101","author":"ZY Bian","year":"2010","unstructured":"Bian ZY, Fan QM, Li G, Xu WT, Tang TT . Human mesenchymal stem cells promote growth of osteosarcoma: involvement of interleukin-6 in the interaction between human mesenchymal stem cells and Saos-2. Cancer Sci 2010; 101: 2554\u20132560.","journal-title":"Cancer Sci"},{"key":"BFcddis2016204_CR9","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/path.4033","volume":"228","author":"QM Fan","year":"2012","unstructured":"Fan QM, Yue B, Bian ZY, Xu WT, Tu B, Dai KR et al. The CREB-Smad6-Runx2 axis contributes to the impaired osteogenesis potential of bone marrow stromal cells in fibrous dysplasia of bone. J Pathol 2012; 228: 45\u201355.","journal-title":"J Pathol"},{"key":"BFcddis2016204_CR10","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.yexcr.2013.10.013","volume":"320","author":"B Tu","year":"2014","unstructured":"Tu B, Peng ZX, Fan QM, Du L, Yan W, Tang TT . Osteosarcoma cells promote the production of pro-tumor cytokines in mesenchymal stem cells by inhibiting their osteogenic differentiation through the TGF-beta\/Smad2\/3 pathway. Exp Cell Res 2014; 320: 164\u2013173.","journal-title":"Exp Cell Res"},{"key":"BFcddis2016204_CR11","doi-asserted-by":"publisher","first-page":"1496","DOI":"10.1016\/j.intimp.2010.06.019","volume":"10","author":"MJ Hoogduijn","year":"2010","unstructured":"Hoogduijn MJ, Popp F, Verbeek R, Masoodi M, Nicolaou A, Baan C et al. The immunomodulatory properties of mesenchymal stem cells and their use for immunotherapy. Int Immunopharmacol 2010; 10: 1496\u20131500.","journal-title":"Int Immunopharmacol"},{"key":"BFcddis2016204_CR12","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/j.immuni.2013.11.010","volume":"39","author":"C Garlanda","year":"2013","unstructured":"Garlanda C, Dinarello CA, Mantovani A . The interleukin-1 family: back to the future. Immunity 2013; 39: 1003\u20131018.","journal-title":"Immunity"},{"key":"BFcddis2016204_CR13","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1111\/j.1600-0765.2009.01204.x","volume":"45","author":"DH Thunell","year":"2010","unstructured":"Thunell DH, Tymkiw KD, Johnson GK, Joly S, Burnell KK, Cavanaugh JE et al. A multiplex immunoassay demonstrates reductions in gingival crevicular fluid cytokines following initial periodontal therapy. J Periodont Res 2010; 45: 148\u2013152.","journal-title":"J Periodont Res"},{"key":"BFcddis2016204_CR14","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1902\/jop.2012.110467","volume":"84","author":"B Cetinkaya","year":"2013","unstructured":"Cetinkaya B, Guzeldemir E, Ogus E, Bulut S . Proinflammatory and anti-inflammatory cytokines in gingival crevicular fluid and serum of patients with rheumatoid arthritis and patients with chronic periodontitis. J Periodontol 2013; 84: 84\u201393.","journal-title":"J Periodontol"},{"key":"BFcddis2016204_CR15","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1172\/JCI200523394","volume":"115","author":"S Wei","year":"2005","unstructured":"Wei S, Kitaura H, Zhou P, Ross FP, Teitelbaum SL . IL-1 mediates TNF-induced osteoclastogenesis. J Clin Invest 2005; 115: 282\u2013290.","journal-title":"J Clin Invest"},{"key":"BFcddis2016204_CR16","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1111\/j.1600-051X.2004.00504.x","volume":"31","author":"A Holmlund","year":"2004","unstructured":"Holmlund A, Hanstrom L, Lerner UH . Bone resorbing activity and cytokine levels in gingival crevicular fluid before and after treatment of periodontal disease. J Clin Periodontol 2004; 31: 475\u2013482.","journal-title":"J Clin Periodontol"},{"key":"BFcddis2016204_CR17","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1111\/j.1365-2362.2011.02545.x","volume":"41","author":"G Schett","year":"2011","unstructured":"Schett G . Effects of inflammatory and anti-inflammatory cytokines on the bone. Eur J Clin Invest 2011; 41: 1361\u20131366.","journal-title":"Eur J Clin Invest"},{"key":"BFcddis2016204_CR18","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1111\/j.1600-0765.2012.01500.x","volume":"48","author":"AS Ertugrul","year":"2013","unstructured":"Ertugrul AS, Sahin H, Dikilitas A, Alpaslan N, Bozoglan A . Comparison of CCL28, interleukin-8, interleukin-1beta and tumor necrosis factor-alpha in subjects with gingivitis, chronic periodontitis and generalized aggressive periodontitis. Journal of periodontal research 2013; 48: 44\u201351.","journal-title":"Journal of periodontal research"},{"key":"BFcddis2016204_CR19","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1902\/jop.2003.74.3.391","volume":"74","author":"DT Graves","year":"2003","unstructured":"Graves DT, Cochran D . The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction. Journal of periodontology 2003; 74: 391\u2013401.","journal-title":"Journal of periodontology"},{"key":"BFcddis2016204_CR20","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1002\/jbmr.5650040116","volume":"4","author":"J Pfeilschifter","year":"1989","unstructured":"Pfeilschifter J, Chenu C, Bird A, Mundy GR, Roodman GD . Interleukin-1 and tumor necrosis factor stimulate the formation of human osteoclastlike cells in vitro. J Bone Miner Res 1989; 4: 113\u2013118.","journal-title":"J Bone Miner Res"},{"key":"BFcddis2016204_CR21","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1186\/ar3380","volume":"13","author":"T Braun","year":"2011","unstructured":"Braun T, Zwerina J . Positive regulators of osteoclastogenesis and bone resorption in rheumatoid arthritis. Arthritis Res Ther 2011; 13: 235.","journal-title":"Arthritis Res Ther"},{"key":"BFcddis2016204_CR22","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1902\/jop.1991.62.8.504","volume":"62","author":"P Stashenko","year":"1991","unstructured":"Stashenko P, Jandinski JJ, Fujiyoshi P, Rynar J, Socransky SS . Tissue levels of bone resorptive cytokines in periodontal disease. J Periodontol 1991; 62: 504\u2013509.","journal-title":"J Periodontol"},{"key":"BFcddis2016204_CR23","doi-asserted-by":"publisher","first-page":"3355","DOI":"10.1002\/art.34555","volume":"64","author":"K Sonomoto","year":"2012","unstructured":"Sonomoto K, Yamaoka K, Oshita K, Fukuyo S, Zhang X, Nakano K et al. Interleukin-1beta induces differentiation of human mesenchymal stem cells into osteoblasts via the Wnt-5a\/receptor tyrosine kinase-like orphan receptor 2 pathway. Arthritis Rheum 2012; 64: 3355\u20133363.","journal-title":"Arthritis Rheum"},{"key":"BFcddis2016204_CR24","doi-asserted-by":"publisher","first-page":"224","DOI":"10.22203\/eCM.v024a16","volume":"24","author":"M Mumme","year":"2012","unstructured":"Mumme M, Scotti C, Papadimitropoulos A, Todorov A, Hoffmann W, Bocelli-Tyndall C et al. Interleukin-1beta modulates endochondral ossification by human adult bone marrow stromal cells. Eur Cell Mater 2012; 24: 224\u2013236.","journal-title":"Eur Cell Mater"},{"key":"BFcddis2016204_CR25","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.jss.2013.06.063","volume":"185","author":"S Deshpande","year":"2013","unstructured":"Deshpande S, James AW, Blough J, Donneys A, Wang SC, Cederna PS et al. Reconciling the effects of inflammatory cytokines on mesenchymal cell osteogenic differentiation. J Surg Res 2013; 185: 278\u2013285.","journal-title":"J Surg Res"},{"key":"BFcddis2016204_CR26","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1016\/j.archoralbio.2011.03.020","volume":"56","author":"L Luo","year":"2011","unstructured":"Luo L, Xie P, Gong P, Tang XH, Ding Y, Deng LX . Expression of HMGB1 and HMGN2 in gingival tissues, GCF and PICF of periodontitis patients and peri-implantitis. Archiv Oral Biol 2011; 56: 1106\u20131111.","journal-title":"Archiv Oral Biol"},{"key":"BFcddis2016204_CR27","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1089\/scd.2013.0345","volume":"23","author":"RL Huang","year":"2014","unstructured":"Huang RL, Yuan Y, Zou GM, Liu G, Tu J, Li Q . LPS-stimulated inflammatory environment inhibits BMP-2-induced osteoblastic differentiation through crosstalk between TLR4\/MyD88\/NF-kappaB and BMP\/Smad signaling. Stem Cells Dev 2014; 23: 277\u2013289.","journal-title":"Stem Cells Dev"},{"key":"BFcddis2016204_CR28","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.yexcr.2016.01.009","volume":"341","author":"L Daigang","year":"2016","unstructured":"Daigang L, Jining Q, Jinlai L, Pengfei W, Chuan S, Liangku H et al. LPS-stimulated inflammation inhibits BMP-9-induced osteoblastic differentiation through crosstalk between BMP\/MAPK and Smad signaling. Exp Cell Res 2016; 341: 54\u201360.","journal-title":"Exp Cell Res"},{"key":"BFcddis2016204_CR29","doi-asserted-by":"publisher","first-page":"272","DOI":"10.7150\/ijbs.2929","volume":"8","author":"G Chen","year":"2012","unstructured":"Chen G, Deng C, Li YP . TGF-beta and BMP signaling in osteoblast differentiation and bone formation. Int J Biol Sci 2012; 8: 272\u2013288.","journal-title":"Int J Biol Sci"},{"key":"BFcddis2016204_CR30","doi-asserted-by":"publisher","first-page":"e7","DOI":"10.1017\/erm.2013.8","volume":"15","author":"T Yucel-Lindberg","year":"2013","unstructured":"Yucel-Lindberg T, Bage T . Inflammatory mediators in the pathogenesis of periodontitis. Expert Rev Mol Med 2013; 15: e7.","journal-title":"Expert Rev Mol Med"},{"key":"BFcddis2016204_CR31","doi-asserted-by":"publisher","first-page":"1430","DOI":"10.1359\/jbmr.2003.18.8.1430","volume":"18","author":"D Magne","year":"2003","unstructured":"Magne D, Bluteau G, Faucheux C, Palmer G, Vignes-Colombeix C, Pilet P et al. Phosphate is a specific signal for ATDC5 chondrocyte maturation and apoptosis-associated mineralization: possible implication of apoptosis in the regulation of endochondral ossification. J Bone Miner Res 2003; 18: 1430\u20131442.","journal-title":"J Bone Miner Res"},{"key":"BFcddis2016204_CR32","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1210\/me.2014-1094","volume":"28","author":"S Hirata-Tsuchiya","year":"2014","unstructured":"Hirata-Tsuchiya S, Fukushima H, Katagiri T, Ohte S, Shin M, Nagano K et al. Inhibition of BMP2-induced bone formation by the p65 subunit of NF-kappaB via an interaction with Smad4. Mol Endocrinol 2014; 28: 1460\u20131470.","journal-title":"Mol Endocrinol"},{"key":"BFcddis2016204_CR33","doi-asserted-by":"publisher","first-page":"35987","DOI":"10.1074\/jbc.M109.070540","volume":"284","author":"M Yamazaki","year":"2009","unstructured":"Yamazaki M, Fukushima H, Shin M, Katagiri T, Doi T, Takahashi T et al. Tumor necrosis factor alpha represses bone morphogenetic protein (BMP) signaling by interfering with the DNA binding of Smads through the activation of NF-kappaB. J Biol Chem 2009; 284: 35987\u201335995.","journal-title":"J Biol Chem"},{"key":"BFcddis2016204_CR34","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1136\/ard.2008.104786","volume":"69","author":"K Polzer","year":"2010","unstructured":"Polzer K, Joosten L, Gasser J, Distler JH, Ruiz G, Baum W et al. Interleukin-1 is essential for systemic inflammatory bone loss. Ann Rheum Dis 2010; 69: 284\u2013290.","journal-title":"Ann Rheum Dis"},{"key":"BFcddis2016204_CR35","doi-asserted-by":"crossref","unstructured":"Loebel C, Czekanska EM, Staudacher J, Salzmann G, Richards RG, Alini M et al. The calcification potential of human MSCs can be enhanced by interleukin-1beta in osteogenic medium. J Tissue Eng Regen Med 2014 (doi:10.1002\/term.1950).","DOI":"10.1002\/term.1950"},{"key":"BFcddis2016204_CR36","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/j.lfs.2009.01.013","volume":"84","author":"J Ding","year":"2009","unstructured":"Ding J, Ghali O, Lencel P, Broux O, Chauveau C, Devedjian JC et al. TNF-alpha and IL-1beta inhibit RUNX2 and collagen expression but increase alkaline phosphatase activity and mineralization in human mesenchymal stem cells. Life Sci 2009; 84: 499\u2013504.","journal-title":"Life Sci"},{"key":"BFcddis2016204_CR37","doi-asserted-by":"publisher","first-page":"1911","DOI":"10.1126\/science.1072682","volume":"298","author":"GL Johnson","year":"2002","unstructured":"Johnson GL, Lapadat R . Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 2002; 298: 1911\u20131912.","journal-title":"Science"},{"key":"BFcddis2016204_CR38","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.tibs.2004.11.009","volume":"30","author":"P Viatour","year":"2005","unstructured":"Viatour P, Merville MP, Bours V, Chariot A . Phosphorylation of NF-kappaB and IkappaB proteins: implications in cancer and inflammation. Trends Biochem Sci 2005; 30: 43\u201352.","journal-title":"Trends Biochem Sci"},{"key":"BFcddis2016204_CR39","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1016\/j.bbrc.2003.08.058","volume":"309","author":"MH Lee","year":"2003","unstructured":"Lee MH, Kwon TG, Park HS, Wozney JM, Ryoo HM . BMP-2-induced Osterix expression is mediated by Dlx5 but is independent of Runx2. Biochem Biophys Res Commun 2003; 309: 689\u2013694.","journal-title":"Biochem Biophys Res Commun"},{"key":"BFcddis2016204_CR40","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1177\/154405910708600403","volume":"86","author":"TA Silva","year":"2007","unstructured":"Silva TA, Garlet GP, Fukada SY, Silva JS, Cunha FQ . Chemokines in oral inflammatory diseases: apical periodontitis and periodontal disease. J Dent Res 2007; 86: 306\u2013319.","journal-title":"J Dent Res"},{"key":"BFcddis2016204_CR41","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1111\/j.1600-0757.2010.00347.x","volume":"53","author":"PM Bartold","year":"2010","unstructured":"Bartold PM, Cantley MD, Haynes DR . Mechanisms and control of pathologic bone loss in periodontitis. Periodontology 2000 2010; 53: 55\u201369.","journal-title":"Periodontology 2000"},{"key":"BFcddis2016204_CR42","first-page":"60","volume":"29","author":"V Deo","year":"2010","unstructured":"Deo V, Bhongade ML . Pathogenesis of periodontitis: role of cytokines in host response. Dentistry today 2010; 29: 60\u201362, 4\u20136; quiz 8\u20139.","journal-title":"Dentistry today"},{"key":"BFcddis2016204_CR43","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1089\/scd.2009.0048","volume":"19","author":"N Huo","year":"2010","unstructured":"Huo N, Tang L, Yang Z, Qian H, Wang Y, Han C et al. Differentiation of dermal multipotent cells into odontogenic lineage induced by embryonic and neonatal tooth germ cell-conditioned medium. Stem Cells Dev 2010; 19: 93\u2013104.","journal-title":"Stem Cells Dev"},{"key":"BFcddis2016204_CR44","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1002\/1529-0131(200105)44:5<1071::AID-ANR187>3.0.CO;2-3","volume":"44","author":"K Johnson","year":"2001","unstructured":"Johnson K, Hashimoto S, Lotz M, Pritzker K, Goding J, Terkeltaub R . Up-regulated expression of the phosphodiesterase nucleotide pyrophosphatase family member PC-1 is a marker and pathogenic factor for knee meniscal cartilage matrix calcification. Arthritis Rheum 2001; 44: 1071\u20131081.","journal-title":"Arthritis Rheum"}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/cddis2016204.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/cddis2016204","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/cddis2016204.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T06:49:01Z","timestamp":1718693341000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/cddis2016204"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,14]]},"references-count":44,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2016,7]]}},"alternative-id":["BFcddis2016204"],"URL":"https:\/\/doi.org\/10.1038\/cddis.2016.204","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,14]]},"assertion":[{"value":"21 March 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 June 2016","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 June 2016","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 July 2016","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}