{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T16:23:57Z","timestamp":1793463837208,"version":"4.5.0"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2006,7,1]],"date-time":"2006-07-01T00:00:00Z","timestamp":1151712000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The role of CTGF\/CCN2 in osteolytic metastasis by breast cancer cells and its mechanism of action were studied. Osteolytic metastasis accompanied by CCN2 and PTHrP overproduction was efficiently inhibited by an anti-CCN2 antibody. Furthermore, we found that CCN2 was induced by PTHrP through PKA-, PKC-, and ERK-mediated pathways therein.<\/jats:p>\n               <jats:p>Introduction: Connective tissue growth factor (CTGF\/CCN2) is a mediator of local angiogenesis induced by breast cancer, but its role in osteolytic metastasis has not been evaluated. PTH-related peptide (PTHrP) is another critical factor in the development of the osteolytic metastasis. Using both in vivo and in vitro approaches, we studied whether\/how neutralization of CCN2 prevented bone metastasis and how PTHrP signaling is related.<\/jats:p>\n               <jats:p>Materials and Methods: A mouse model of bone metastasis by human breast cancer cell line MDA231 was treated with a CCN2-neutralizing antibody, and osteolytic bone metastases were assessed on radiographs and immunohistochemistry. Ccn2 gene expression and transcription were examined by Northern blot and luciferase analysis. Immunoblot analysis and kinase inhibitors were used to identify the signaling pathways implicated. Anti-angiogenic\/osteoclastogenic effects of ccn2 downregulation were also evaluated.<\/jats:p>\n               <jats:p>Results: Treatment of mice with a CCN2-neutralizing antibody greatly decreased osteolytic bone metastasis, microvasculature, and osteoclasts involved. The antibody also suppressed the growth of subcutaneous tumor in vivo and proliferation and migration of human umbilical vein endothelial cells (HUVECs) in vitro. Downregulation of ccn2 also repressed osteoclastogenesis. CCN2 expression was specifically observed in cancer cells producing PTHrP and type I PTH\/PTHrP receptor (PTH1R) invaded the bone marrow, and PTHrP strongly upregulated ccn2 in MDA231 cells in vitro. Activation of protein kinase C (PKC) and protein kinase A (PKA) was necessary and sufficient for the stimulation of ccn2 by PTHrP. Indeed, inhibition of the extracellular signal-regulated kinase (ERK1\/2), PKC, or PKA by specific inhibitors counteracted the stimulation of ccn2 expression. Incubation of MDA231 cells with PTHrP induced the activation of ERK1\/2. Consistent with these findings, inhibition of PKC prevented PTHrP-induced ERK1\/2 activation, whereas 12-O-tetradecanoylphorbol13-acetate (TPA), a stimulator of PKC, upregulated it.<\/jats:p>\n               <jats:p>Conclusions: CCN2 was critically involved in osteolytic metastasis and was induced by PKA- and PKC-dependent activation of ERK1\/2 signaling by PTHrP. Thus, CCN2 may be a new molecular target for anti-osteolytic therapy to shut off the PTHrP\u2013CCN2 signaling pathway.<\/jats:p>","DOI":"10.1359\/jbmr.060416","type":"journal-article","created":{"date-parts":[[2006,7,4]],"date-time":"2006-07-04T05:47:20Z","timestamp":1151992040000},"page":"1045-1059","source":"Crossref","is-referenced-by-count":149,"title":["Pathogenic Role of Connective Tissue Growth Factor (CTGF\/CCN2) in Osteolytic Metastasis of Breast Cancer"],"prefix":"10.1093","volume":"21","author":[{"given":"Tsuyoshi","family":"Shimo","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery and Biopathological Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Kubota","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norie","family":"Yoshioka","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery and Biopathological Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soichiro","family":"Ibaragi","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery and Biopathological Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiko","family":"Isowa","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery and Biopathological Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Eguchi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery and Biopathological Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaharu","family":"Takigawa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,4]]},"reference":[{"key":"2024013019384589100_bib1","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/S0959-8049(97)10132-0","article-title":"Cellular and molecular mechanisms of breast and prostate cancer metastasis to bone","volume":"34","author":"Yoneda","year":"1998","journal-title":"Eur J Cancer"},{"key":"2024013019384589100_bib2","first-page":"18","article-title":"Cancer and bone","volume":"19","author":"Guise","year":"1998","journal-title":"Endocr Rev"},{"key":"2024013019384589100_bib3","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.bbrc.2004.11.070","article-title":"Crosstalk between cancer cells and bone microenvironment in bone metastasis","volume":"328","author":"Yoneda","year":"2005","journal-title":"Biochem Biophys Res Commun"},{"key":"2024013019384589100_bib4","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/S0092-8674(00)80108-7","article-title":"Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis","volume":"86","author":"Hanahan","year":"1996","journal-title":"Cell"},{"key":"2024013019384589100_bib5","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1007\/PL00008475","article-title":"Human breast cancer cells induced angiogenesis, recruitment, and activation of osteoclasts in osteolytic metastasis","volume":"126","author":"Winding","year":"2000","journal-title":"J Cancer Res Clin Oncol"},{"key":"2024013019384589100_bib6","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1053\/ctrv.1999.0143","article-title":"Tumour progression and angiogenesis in bone metastasis from breast cancer: New approaches to an old problem","volume":"26","author":"Pluijm","year":"2000","journal-title":"Cancer Treat Rev"},{"key":"2024013019384589100_bib7","first-page":"462","article-title":"Angiogenesis inhibitor TNP-470 inhibits human breast cancer osteolytic bone metastasis in nude mice through the reduction of bone resorption","volume":"58","author":"Sasaki","year":"1998","journal-title":"Cancer Res"},{"key":"2024013019384589100_bib8","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/0014-5793(93)80155-N","article-title":"The modular architecture of a new family of growth regulators related to connective tissue growth factor","volume":"327","author":"Bork","year":"1993","journal-title":"FEBS Lett"},{"key":"2024013019384589100_bib9","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S1359-6101(97)00010-5","article-title":"Connective tissue growth factor: A mediator of TGF-beta action on fibroblasts","volume":"8","author":"Grotendorst","year":"1997","journal-title":"Cytokine Growth Factor Rev"},{"key":"2024013019384589100_bib10","first-page":"189","article-title":"The connective tissue growth factor\/cysteine-rich 61\/nephroblastoma overexpressed (CCN) family","volume":"20","author":"Brigstock","year":"1999","journal-title":"Endocr Rev"},{"key":"2024013019384589100_bib11","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1210\/endo.141.1.7267","article-title":"Effects of CTGF\/Hcs24, a product of a hypertrophic chondrocyte-specific gene, on the proliferation and differentiation of chondrocytes in culture","volume":"141","author":"Nakanishi","year":"2000","journal-title":"Endocrinology"},{"key":"2024013019384589100_bib12","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/ncb826","article-title":"Connective-tissue growth factor (CTGF) modulates cell signalling by BMP and TGF-beta","volume":"4","author":"Abreu","year":"2002","journal-title":"Nat Cell Biol"},{"key":"2024013019384589100_bib13","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1358\/dnp.2003.16.1.829302","article-title":"CTGF\/Hcs24 as a multifunctional growth factor for fibroblasts, chondrocytes and vascular endothelial cells","volume":"16","author":"Takigawa","year":"2003","journal-title":"Drug News Perspect"},{"key":"2024013019384589100_bib14","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1002\/jcp.10206","article-title":"Role of CTGF\/HCS24\/ecogenin in skeletal growth control","volume":"194","author":"Takigawa","year":"2003","journal-title":"J Cell Physiol"},{"key":"2024013019384589100_bib15","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1093\/oxfordjournals.jbchem.a022071","article-title":"Inhibition of endogenous expression of connective tissue growth factor by its antisense oligonucleotide and antisense RNA suppresses proliferation and migration of vascular endothelial cells","volume":"124","author":"Shimo","year":"1998","journal-title":"J Biochem (Tokyo)"},{"key":"2024013019384589100_bib16","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1093\/oxfordjournals.jbchem.a022414","article-title":"Connective tissue growth factor induces the proliferation, migration, and tube formation of vascular endothelial cells in vitro, and angiogenesis in vivo","volume":"126","author":"Shimo","year":"1999","journal-title":"J Biochem (Tokyo)"},{"key":"2024013019384589100_bib17","doi-asserted-by":"crossref","first-page":"2779","DOI":"10.1242\/dev.00505","article-title":"Connective tissue growth factor coordinates chondrogenesis and angiogenesis during skeletal development","volume":"130","author":"Ivkovic","year":"2003","journal-title":"Development"},{"key":"2024013019384589100_bib18","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1159\/000055339","article-title":"Involvement of CTGF, a hypertrophic chondrocyte-specific gene product, in tumor angiogenesis","volume":"61","author":"Shimo","year":"2001","journal-title":"Oncology"},{"key":"2024013019384589100_bib19","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S1535-6108(03)00132-6","article-title":"A multigenic program mediating breast cancer metastasis to bone","volume":"3","author":"Kang","year":"2003","journal-title":"Cancer Cell"},{"key":"2024013019384589100_bib20","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1111\/1523-1747.ep12313452","article-title":"Growth regulation in scleroderma fibroblasts: Increased response to transforming growth factor-beta 1","volume":"105","author":"Kikuchi","year":"1995","journal-title":"J Invest Dermatol"},{"key":"2024013019384589100_bib21","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1053\/ajkd.2001.27422","article-title":"Role of connective tissue growth factor in profibrotic action of transforming growth factor-beta: A potential target for preventing renal fibrosis","volume":"38","author":"Yokoi","year":"2001","journal-title":"Am J Kidney Dis"},{"key":"2024013019384589100_bib22","doi-asserted-by":"crossref","first-page":"8887","DOI":"10.1158\/0008-5472.CAN-05-1702","article-title":"Stromal expression of connective tissue growth factor promotes angiogenesis and prostate cancer tumorigenesis","volume":"65","author":"Yang","year":"2005","journal-title":"Cancer Res"},{"key":"2024013019384589100_bib23","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1172\/JCI118947","article-title":"Evidence for a causal role of parathyroid hormone-related protein in the pathogenesis of human breast cancer-mediated osteolysis","volume":"98","author":"Guise","year":"1996","journal-title":"J Clin Invest"},{"key":"2024013019384589100_bib24","first-page":"3817","article-title":"Humanized monoclonal antibody against parathyroid hormone-related protein suppresses osteolytic bone metastasis of human breast cancer cells derived from MDA-MB-231","volume":"25","author":"Saito","year":"2005","journal-title":"Anticancer Res"},{"key":"2024013019384589100_bib25","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1158\/0008-5472.CAN-05-2814","article-title":"Parathyroid hormone-related protein localization in breast cancers predict improved prognosis","volume":"66","author":"Henderson","year":"2006","journal-title":"Cancer Res"},{"key":"2024013019384589100_bib26","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1152\/ajpendo.00131.2002","article-title":"Cyr61 and CTGF are molecular markers of bladder wall remodeling after outlet obstruction","volume":"283","author":"Chaqour","year":"2002","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2024013019384589100_bib27","doi-asserted-by":"crossref","first-page":"2732","DOI":"10.1073\/pnas.89.7.2732","article-title":"Expression cloning of a common receptor for parathyroid hormone and parathyroid hormone-related peptide from rat osteoblast-like cells: A single receptor stimulates intracellular accumulation of both cAMP and inositol trisphosphates and increases intracellular free calcium","volume":"89","author":"Abou-Samra","year":"1992","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024013019384589100_bib28","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1126\/science.1658941","article-title":"A G protein-linked receptor for parathyroid hormone and parathyroid hormone-related peptide","volume":"254","author":"Juppner","year":"1991","journal-title":"Science"},{"key":"2024013019384589100_bib29","first-page":"665","article-title":"Receptors for PTH and PTHrP: Their biological importance and functional properties","volume":"277","author":"Mannstadt","year":"1999","journal-title":"Am J Physiol"},{"key":"2024013019384589100_bib30","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.2174\/092986730611220401164817","article-title":"Design and applications of parathyroid hormone analogues","volume":"6","author":"Morley","year":"1999","journal-title":"Curr Med Chem"},{"key":"2024013019384589100_bib31","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1359\/jbmr.1999.14.2.173","article-title":"Interactions of PTH and PTHrP with the PTH\/PTHrP receptor and with downstream signaling pathways: Exceptions that provide the rules","volume":"14","author":"Goltzman","year":"1999","journal-title":"J Bone Miner Res"},{"key":"2024013019384589100_bib32","doi-asserted-by":"crossref","first-page":"3423","DOI":"10.1074\/jbc.272.6.3423","article-title":"Parathyroid hormone activates mitogen-activated protein kinase via a cAMP-mediated pathway independent of Ras","volume":"272","author":"Verheijen","year":"1997","journal-title":"J Biol Chem"},{"key":"2024013019384589100_bib33","doi-asserted-by":"crossref","first-page":"7586","DOI":"10.1074\/jbc.M007400200","article-title":"Stimulation of extracellular signal-regulated kinases and proliferation in rat osteoblastic cells by parathyroid hormone is protein kinase C-dependent","volume":"276","author":"Swarthout","year":"2001","journal-title":"J Biol Chem"},{"key":"2024013019384589100_bib34","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1074\/jbc.273.4.1839","article-title":"The pathways connecting G protein-coupled receptors to the nucleus through divergent mitogen-activated protein kinase cascades","volume":"273","author":"Gutkind","year":"1998","journal-title":"J Biol Chem"},{"key":"2024013019384589100_bib35","first-page":"2665","article-title":"Generation of a humanized monoclonal antibody against human parathyroid hormone-related protein and its efficacy against humoral hypercalcemia of malignancy","volume":"24","author":"Onuma","year":"2004","journal-title":"Anticancer Res"},{"key":"2024013019384589100_bib36","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1089\/104454903770238111","article-title":"Novel enzyme-linked immunosorbent assay systems for the quantitative analysis of connective tissue growth factor (CTGF\/Hcs24\/CCN2): Detection of HTLV-I tax-induced CTGF from a human carcinoma cell line","volume":"22","author":"Kawaki","year":"2003","journal-title":"DNA Cell Biol"},{"key":"2024013019384589100_bib37","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1093\/oxfordjournals.jbchem.a002965","article-title":"Regulatory mechanism of human connective tissue growth factor (CTGF\/Hcs24) gene expression in a human chondrocytic cell line, HCS-2\/8","volume":"130","author":"Eguchi","year":"2001","journal-title":"J Biochem (Tokyo)"},{"key":"2024013019384589100_bib38","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1093\/jnci\/53.3.661","article-title":"Breast tumor cell lines from pleural effusions","volume":"53","author":"Cailleau","year":"1974","journal-title":"J Natl Cancer Inst"},{"key":"2024013019384589100_bib39","first-page":"3551","article-title":"Bisphosphonate risedronate reduces metastatic human breast cancer burden in bone in nude mice","volume":"55","author":"Sasaki","year":"1995","journal-title":"Cancer Res"},{"key":"2024013019384589100_bib40","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1002\/dvdy.20109","article-title":"Expression and roles of connective tissue growth factor in Meckel's cartilage development","volume":"231","author":"Shimo","year":"2004","journal-title":"Dev Dyn"},{"key":"2024013019384589100_bib41","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0304-3835(01)00683-8","article-title":"Connective tissue growth factor as a major angiogenic agent that is induced by hypoxia in a human breast cancer cell line","volume":"174","author":"Shimo","year":"2001","journal-title":"Cancer Lett"},{"key":"2024013019384589100_bib42","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1002\/dvdy.20009","article-title":"Indian hedgehog and syndecans-3 coregulate chondrocyte proliferation and function during chick limb skeletogenesis","volume":"229","author":"Shimo","year":"2004","journal-title":"Dev Dyn"},{"key":"2024013019384589100_bib43","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/0090-8258(86)90026-0","article-title":"The inhibitory effect of tranexamic acid on human ovarian carcinoma cell grown in vitro and in vivo.","volume":"24","author":"Kikuchi","year":"1986","journal-title":"Gynecol Oncol"},{"key":"2024013019384589100_bib44","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1210\/endo-122-4-1373","article-title":"Osteoclast-like cell formation and its regulation by osteotropic hormones in mouse bone marrow cultures","volume":"122","author":"Takahashi","year":"1988","journal-title":"Endocrinology"},{"key":"2024013019384589100_bib45","doi-asserted-by":"crossref","first-page":"24571","DOI":"10.1074\/jbc.M202561200","article-title":"Transforming growth factor-beta stimulates parathyroid hormone-related protein and osteolytic metastases via Smad and mitogen-activated protein kinase signaling pathways","volume":"277","author":"Kakonen","year":"2002","journal-title":"J Biol Chem"},{"key":"2024013019384589100_bib46","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0076-6879(97)82110-6","article-title":"Role of 1 alpha,25-dihydroxyvitamin D3 in osteoclast differentiation and function","volume":"282","author":"Suda","year":"1997","journal-title":"Methods Enzymol"},{"key":"2024013019384589100_bib47","doi-asserted-by":"crossref","first-page":"12665","DOI":"10.1016\/S0021-9258(18)67143-1","article-title":"Growth factors in bone matrix. Isolation of multiple types by affinity chromatography on heparin-Sepharose","volume":"261","author":"Hauschka","year":"1986","journal-title":"J Biol Chem"},{"key":"2024013019384589100_bib48","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1073\/pnas.84.7.2024","article-title":"Modulation of type beta transforming growth factor activity in bone cultures by osteotropic hormones","volume":"84","author":"Pfeilschifter","year":"1987","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024013019384589100_bib49","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1210\/endo-125-4-1805","article-title":"The bone marrow-derived stromal cell lines MC3T3-G2\/PA6 and ST2 support osteoclast-like cell differentiation in cocultures with mouse spleen cells","volume":"125","author":"Udagawa","year":"1989","journal-title":"Endocrinology"},{"key":"2024013019384589100_bib50","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1093\/carcin\/23.5.769","article-title":"Connective tissue growth factor increased by hypoxia may initiate angiogenesis in collaboration with matrix metalloproteinases","volume":"23","author":"Kondo","year":"2002","journal-title":"Carcinogenesis"},{"key":"2024013019384589100_bib51","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1016\/S0006-2952(02)00990-5","article-title":"Molecular cloning and pharmacological characterization of bovine calcitonin receptor-like receptor from bovine aortic endothelial cells","volume":"63","author":"Aiyar","year":"2002","journal-title":"Biochem Pharmacol"},{"key":"2024013019384589100_bib52","doi-asserted-by":"crossref","first-page":"45826","DOI":"10.1074\/jbc.M309024200","article-title":"Angiostatin inhibits bone metastasis formation in nude mice through a direct anti-osteoclastic activity","volume":"278","author":"Peyruchaud","year":"2003","journal-title":"J Biol Chem"},{"key":"2024013019384589100_bib53","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1002\/1097-4652(200008)184:2<197::AID-JCP7>3.0.CO;2-R","article-title":"Effects of CTGF\/Hcs24, a hypertrophic chondrocyte-specific gene product, on the proliferation and differentiation of osteoblastic cells in vitro","volume":"184","author":"Nishida","year":"2000","journal-title":"J Cell Physiol"},{"key":"2024013019384589100_bib54","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/jcp.10319","article-title":"Expression of connective tissue growth factor in bone: Its role in osteoblast proliferation and differentiation in vitro and bone formation in vivo","volume":"196","author":"Safadi","year":"2003","journal-title":"J Cell Physiol"},{"key":"2024013019384589100_bib55","doi-asserted-by":"crossref","first-page":"55958","DOI":"10.1074\/jbc.M407810200","article-title":"Connective tissue growth factor (CTGF) is regulated by Wnt and bone morphogenetic proteins signaling in osteoblast differentiation of mesenchymal stem cells","volume":"279","author":"Luo","year":"2004","journal-title":"J Biol Chem"},{"key":"2024013019384589100_bib56","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.bone.2005.10.005","article-title":"Expression and regulation of CCN genes in murine osteoblasts","volume":"38","author":"Parisi","year":"2006","journal-title":"Bone"},{"key":"2024013019384589100_bib57","doi-asserted-by":"crossref","first-page":"2958","DOI":"10.1128\/MCB.19.4.2958","article-title":"Fisp12\/mouse connective tissue growth factor mediates endothelial cell adhesion and migration through integrin alphavbeta3, promotes endothelial cell survival, and induces angiogenesis in vivo","volume":"19","author":"Babic","year":"1999","journal-title":"Mol Cell Biol"},{"key":"2024013019384589100_bib58","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1074\/jbc.M402550200","article-title":"Apoptosis and survival of osteoblast-like cells are regulated by surface attachment","volume":"280","author":"Grigoriou","year":"2005","journal-title":"J Biol Chem"},{"key":"2024013019384589100_bib59","doi-asserted-by":"crossref","first-page":"4335","DOI":"10.1182\/blood.V96.13.4335","article-title":"An adherent condition is required for formation of multinuclear osteoclasts in the presence of macrophage colony-stimulating factor and receptor activator of nuclear factor kappa B ligand","volume":"96","author":"Miyamoto","year":"2000","journal-title":"Blood"},{"key":"2024013019384589100_bib60","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1002\/path.1468","article-title":"NOV (CCN3) regulation in the growth plate and CCN family member expression in cartilage neoplasia","volume":"201","author":"Yu","year":"2003","journal-title":"J Pathol"},{"key":"2024013019384589100_bib61","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1002\/(SICI)1097-0142(19971015)80:8+<1572::AID-CNCR7>3.0.CO;2-M","article-title":"Parathyroid hormone-related protein and bone metastases","volume":"80","author":"Guise","year":"1997","journal-title":"Cancer"},{"key":"2024013019384589100_bib62","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1359\/jbmr.2001.16.6.1077","article-title":"Monitoring metastatic behavior of human tumor cells in mice with species-specific polymerase chain reaction: Elevated expression of angiogenesis and bone resorption stimulators by breast cancer in bone metastases","volume":"16","author":"van der Pluijm","year":"2001","journal-title":"J Bone Miner Res"},{"key":"2024013019384589100_bib63","doi-asserted-by":"crossref","first-page":"32204","DOI":"10.1074\/jbc.M101084200","article-title":"Parathyroid hormone-related peptide stimulates osteogenic cell proliferation through protein kinase C activation of the Ras\/mitogen-activated protein kinase signaling pathway","volume":"276","author":"Miao","year":"2001","journal-title":"J Biol Chem"},{"key":"2024013019384589100_bib64","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1006\/bbrc.1994.1224","article-title":"Direct involvement of cAMP-dependent protein kinase in the regulation of alkaline phosphatase activity by parathyroid hormone (PTH) and PTH-related peptide in osteoblastic UMR-106 cells","volume":"28","author":"Kano","year":"1994","journal-title":"Biochem Biophys Res Commun"},{"key":"2024013019384589100_bib65","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1126\/science.275.5298.394","article-title":"Linkage of G protein-coupled receptors to the MAPK signaling pathway through PI 3-kinase gamma","volume":"275","author":"Lopez-Ilasaca","year":"1997","journal-title":"Science"},{"key":"2024013019384589100_bib66","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1124\/mol.54.3.453","article-title":"D1 dopamine receptor agonists mediate activation of p38 mitogen-activated protein kinase and c-Jun amino-terminal kinase by a protein kinase A-dependent mechanism in SK-N-MC human neuroblastoma cells","volume":"54","author":"Zhen","year":"1998","journal-title":"Mol Pharmacol"},{"key":"2024013019384589100_bib67","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1146\/annurev.bi.60.070191.003253","article-title":"Model systems for the study of seven-transmembrane-segment receptors","volume":"60","author":"Dohlman","year":"1991","journal-title":"Annu Rev Biochem"},{"key":"2024013019384589100_bib68","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S1097-2765(01)00432-4","article-title":"PKA phosphorylation of Src mediates cAMP's inhibition of cell growth via Rap1","volume":"9","author":"Schmitt","year":"2002","journal-title":"Mol Cell"}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1359%2Fjbmr.060416","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/21\/7\/1045\/56480098\/5650210708.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/21\/7\/1045\/56480098\/5650210708.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T14:46:49Z","timestamp":1710341209000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/21\/7\/1045-1059\/7593357"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,7,1]]},"references-count":68,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2009,12,4]]},"published-print":{"date-parts":[[2006,7,1]]}},"URL":"https:\/\/doi.org\/10.1359\/jbmr.060416","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2006,7,1]]},"published":{"date-parts":[[2006,7,1]]}}}