{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:02:37Z","timestamp":1791241357582,"version":"4.1.0"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2014,7,6]],"date-time":"2014-07-06T00:00:00Z","timestamp":1404604800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2014,7,6]],"date-time":"2014-07-06T00:00:00Z","timestamp":1404604800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2014,8]]},"DOI":"10.1038\/nm.3583","type":"journal-article","created":{"date-parts":[[2014,7,6]],"date-time":"2014-07-06T19:52:18Z","timestamp":1404676338000},"page":"904-910","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Asfotase-\u03b1 improves bone growth, mineralization and strength in mouse models of neurofibromatosis type-1"],"prefix":"10.1038","volume":"20","author":[{"given":"Jean","family":"de la Croix Ndong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J","family":"Makowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasidhar","family":"Uppuganti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Vignaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichiro","family":"Ono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel S","family":"Perrien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Joubert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena R","family":"Baglio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Granchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Stevenson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan J","family":"Rios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffry S","family":"Nyman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2972-5633","authenticated-orcid":false,"given":"Florent","family":"Elefteriou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,7,6]]},"reference":[{"key":"BFnm3583_CR1","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1136\/jmg.26.11.704","volume":"26","author":"SM Huson","year":"1989","unstructured":"Huson, S.M., Compston, D.A., Clark, P. & Harper, P.S. A genetic study of von Recklinghausen neurofibromatosis in south east Wales. I. Prevalence, fitness, mutation rate, and effect of parental transmission on severity. J. Med. Genet. 26, 704\u2013711 (1989).","journal-title":"J. Med. Genet."},{"key":"BFnm3583_CR2","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1097\/BPO.0b013e31828121b8","volume":"33","author":"DA Stevenson","year":"2013","unstructured":"Stevenson, D.A. et al. Approaches to treating NF1 tibial pseudarthrosis: consensus from the Children's Tumor Foundation NF1 Bone Abnormalities Consortium. J. Pediatr. Orthop. 33, 269\u2013275 (2013).","journal-title":"J. Pediatr. Orthop."},{"key":"BFnm3583_CR3","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1002\/ajmg.a.33045","volume":"149A","author":"F Elefteriou","year":"2009","unstructured":"Elefteriou, F. et al. Skeletal abnormalities in neurofibromatosis type 1: approaches to therapeutic options. Am. J. Med. Genet. A. 149A, 2327\u20132338 (2009).","journal-title":"Am. J. Med. Genet. A."},{"key":"BFnm3583_CR4","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1007\/s00198-004-1801-4","volume":"16","author":"T Kuorilehto","year":"2005","unstructured":"Kuorilehto, T. et al. Decreased bone mineral density and content in neurofibromatosis type 1: lowest local values are located in the load-carrying parts of the body. Osteoporos. Int. 16, 928\u2013936 (2005).","journal-title":"Osteoporos. Int."},{"key":"BFnm3583_CR5","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jpeds.2006.10.048","volume":"150","author":"DA Stevenson","year":"2007","unstructured":"Stevenson, D.A. et al. Bone mineral density in children and adolescents with neurofibromatosis type 1. J. Pediatr. 150, 83\u201388 (2007).","journal-title":"J. Pediatr."},{"key":"BFnm3583_CR6","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.braindev.2008.02.002","volume":"30","author":"O Duman","year":"2008","unstructured":"Duman, O. et al. Bone metabolism markers and bone mineral density in children with neurofibromatosis type-1. Brain Dev. 30, 584\u2013588 (2008).","journal-title":"Brain Dev."},{"key":"BFnm3583_CR7","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1097\/00003086-200208000-00013","volume":"401","author":"MG Vitale","year":"2002","unstructured":"Vitale, M.G., Guha, A. & Skaggs, D.L. Orthopaedic manifestations of neurofibromatosis in children: an update. Clin. Orthop. Relat. Res. 401, 107\u2013118 (2002).","journal-title":"Clin. Orthop. Relat. Res."},{"key":"BFnm3583_CR8","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1002\/(SICI)1096-8628(19990611)84:5<413::AID-AJMG5>3.0.CO;2-1","volume":"84","author":"DA Stevenson","year":"1999","unstructured":"Stevenson, D.A. et al. Descriptive analysis of tibial pseudarthrosis in patients with neurofibromatosis 1. Am. J. Med. Genet. 84, 413\u2013419 (1999).","journal-title":"Am. J. Med. Genet."},{"key":"BFnm3583_CR9","first-page":"119","volume":"153","author":"HR Neitzschman","year":"2001","unstructured":"Neitzschman, H.R., Costelloe, C.M., Willis, R.B. & De Mouy, E.H. Radiology case of the month. Congenital bone disorder associated with deformity, fracture, and pseudoarthrosis. Congenital tibial dysplasia\u2013neurofibromatosis type I (NF1). J. La. State Med. Soc. 153, 119\u2013121 (2001).","journal-title":"J. La. State Med. Soc."},{"key":"BFnm3583_CR10","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1097\/01202412-200001000-00002","volume":"9","author":"E Ippolito","year":"2000","unstructured":"Ippolito, E., Corsi, A., Grill, F., Wientroub, S. & Bianco, P. Pathology of bone lesions associated with congenital pseudarthrosis of the leg. J. Pediatr. Orthop. B 9, 3\u201310 (2000).","journal-title":"J. Pediatr. Orthop. B"},{"key":"BFnm3583_CR11","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1086\/504441","volume":"79","author":"DA Stevenson","year":"2006","unstructured":"Stevenson, D.A. et al. Double inactivation of NF1 in tibial pseudarthrosis. Am. J. Hum. Genet. 79, 143\u2013148 (2006).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnm3583_CR12","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1093\/hmg\/ddm032","volume":"16","author":"M Kolanczyk","year":"2007","unstructured":"Kolanczyk, M. et al. Multiple roles for neurofibromin in skeletal development and growth. Hum. Mol. Genet. 16, 874\u2013886 (2007).","journal-title":"Hum. Mol. Genet."},{"key":"BFnm3583_CR13","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1016\/j.bone.2011.09.043","volume":"49","author":"K Sullivan","year":"2011","unstructured":"Sullivan, K., El-Hoss, J., Little, D.G. & Schindeler, A. JNK inhibitors increase osteogenesis in Nf1-deficient cells. Bone 49, 1311\u20131316 (2011).","journal-title":"Bone"},{"key":"BFnm3583_CR14","doi-asserted-by":"crossref","first-page":"230","DOI":"10.4055\/cios.2011.3.3.230","volume":"3","author":"DY Lee","year":"2011","unstructured":"Lee, D.Y. et al. Disturbed osteoblastic differentiation of fibrous hamartoma cell from congenital pseudarthrosis of the tibia associated with neurofibromatosis type I. Clin. Orthop. Surg. 3, 230\u2013237 (2011).","journal-title":"Clin. Orthop. Surg."},{"key":"BFnm3583_CR15","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.bone.2008.10.050","volume":"44","author":"HV Leskel\u00e4","year":"2009","unstructured":"Leskel\u00e4, H.V. et al. Congenital pseudarthrosis of neurofibromatosis type 1: impaired osteoblast differentiation and function and altered NF1 gene expression. Bone 44, 243\u2013250 (2009).","journal-title":"Bone"},{"key":"BFnm3583_CR16","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1093\/hmg\/ddl208","volume":"15","author":"X Wu","year":"2006","unstructured":"Wu, X. et al. Neurofibromin plays a critical role in modulating osteoblast differentiation of mesenchymal stem\/progenitor cells. Hum. Mol. Genet. 15, 2837\u20132845 (2006).","journal-title":"Hum. Mol. Genet."},{"key":"BFnm3583_CR17","doi-asserted-by":"crossref","first-page":"e86115","DOI":"10.1371\/journal.pone.0086115","volume":"9","author":"J K\u00fchnisch","year":"2014","unstructured":"K\u00fchnisch, J. et al. Multiscale, converging defects of macro-porosity, microstructure and matrix mineralization impact long bone fragility in NF1. PLoS ONE 9, e86115 (2014).","journal-title":"PLoS ONE"},{"key":"BFnm3583_CR18","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.cmet.2006.10.010","volume":"4","author":"F Elefteriou","year":"2006","unstructured":"Elefteriou, F. et al. ATF4 mediation of NF1 functions in osteoblast reveals a nutritional basis for congenital skeletal dysplasiae. Cell Metab. 4, 441\u2013451 (2006).","journal-title":"Cell Metab."},{"key":"BFnm3583_CR19","doi-asserted-by":"crossref","first-page":"2476","DOI":"10.1002\/jbmr.1992","volume":"28","author":"SD Rhodes","year":"2013","unstructured":"Rhodes, S.D. et al. Hyperactive transforming growth factor-\u03b21 signaling potentiates skeletal defects in a neurofibromatosis type 1 mouse model. J. Bone Miner. Res. 28, 2476\u20132489 (2013).","journal-title":"J. Bone Miner. Res."},{"key":"BFnm3583_CR20","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s00198-009-0933-y","volume":"21","author":"S Seitz","year":"2010","unstructured":"Seitz, S. et al. High bone turnover and accumulation of osteoid in patients with neurofibromatosis 1. Osteoporos. Int. 21, 119\u2013127 (2010).","journal-title":"Osteoporos. Int."},{"key":"BFnm3583_CR21","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1359\/jbmr.2003.18.6.994","volume":"18","author":"K Johnson","year":"2003","unstructured":"Johnson, K. et al. Linked deficiencies in extracellular PPi and osteopontin mediate pathologic calcification associated with defective PC-1 and ANK expression. J. Bone Miner. Res. 18, 994\u20131004 (2003).","journal-title":"J. Bone Miner. Res."},{"key":"BFnm3583_CR22","doi-asserted-by":"crossref","first-page":"C1","DOI":"10.1152\/ajpcell.2001.281.1.C1","volume":"281","author":"RA Terkeltaub","year":"2001","unstructured":"Terkeltaub, R.A. Inorganic pyrophosphate generation and disposition in pathophysiology. Am. J. Physiol. Cell Physiol. 281, C1\u2013C11 (2001).","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"BFnm3583_CR23","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1016\/j.bone.2009.12.018","volume":"46","author":"VE Macrae","year":"2010","unstructured":"Macrae, V.E. et al. Inhibition of PHOSPHO1 activity results in impaired skeletal mineralization during limb development of the chick. Bone 46, 1146\u20131155 (2010).","journal-title":"Bone"},{"key":"BFnm3583_CR24","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/S0002-9440(10)63208-7","volume":"164","author":"D Harmey","year":"2004","unstructured":"Harmey, D. et al. Concerted regulation of inorganic pyrophosphate and osteopontin by Akp2, Enpp1, and Ank: an integrated model of the pathogenesis of mineralization disorders. Am. J. Pathol. 164, 1199\u20131209 (2004).","journal-title":"Am. J. Pathol."},{"key":"BFnm3583_CR25","doi-asserted-by":"crossref","first-page":"15872","DOI":"10.1074\/jbc.M701116200","volume":"282","author":"WN Addison","year":"2007","unstructured":"Addison, W.N., Azari, F., Sorensen, E.S., Kaartinen, M.T. & McKee, M.D. Pyrophosphate inhibits mineralization of osteoblast cultures by binding to mineral, up-regulating osteopontin, and inhibiting alkaline phosphatase activity. J. Biol. Chem. 282, 15872\u201315883 (2007).","journal-title":"J. Biol. Chem."},{"key":"BFnm3583_CR26","doi-asserted-by":"crossref","first-page":"36024","DOI":"10.1074\/jbc.M206030200","volume":"277","author":"H Sowa","year":"2002","unstructured":"Sowa, H., Kaji, H., Yamaguchi, T., Sugimoto, T. & Chihara, K. Activations of ERK1\/2 and JNK by transforming growth factor beta negatively regulate Smad3-induced alkaline phosphatase activity and mineralization in mouse osteoblastic cells. J. Biol. Chem. 277, 36024\u201336031 (2002).","journal-title":"J. Biol. Chem."},{"key":"BFnm3583_CR27","doi-asserted-by":"crossref","first-page":"35975","DOI":"10.1074\/jbc.M112.372458","volume":"287","author":"N Lian","year":"2012","unstructured":"Lian, N. et al. Transforming growth factor \u03b2 suppresses osteoblast differentiation via the vimentin activating transcription factor 4 (ATF4) axis. J. Biol. Chem. 287, 35975\u201335984 (2012).","journal-title":"J. Biol. Chem."},{"key":"BFnm3583_CR28","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1359\/jbmr.1998.13.6.931","volume":"13","author":"RA Terkeltaub","year":"1998","unstructured":"Terkeltaub, R.A. et al. Bone morphogenetic proteins and bFGF exert opposing regulatory effects on PTHrP expression and inorganic pyrophosphate elaboration in immortalized murine endochondral hypertrophic chondrocytes (MCT cells). J. Bone Miner. Res. 13, 931\u2013941 (1998).","journal-title":"J. Bone Miner. Res."},{"key":"BFnm3583_CR29","doi-asserted-by":"crossref","first-page":"2890","DOI":"10.1074\/mcp.M112.024927","volume":"12","author":"RD Alves","year":"2013","unstructured":"Alves, R.D., Eijken, M., Bezstarosti, K., Demmers, J.A. & van Leeuwen, J.P. Activin A suppresses osteoblast mineralization capacity by altering extracellular matrix composition and impairing matrix vesicle production. Mol. Cell. Proteomics 12, 2890\u20132900 (2013).","journal-title":"Mol. Cell. Proteomics"},{"key":"BFnm3583_CR30","doi-asserted-by":"crossref","first-page":"44005","DOI":"10.1074\/jbc.M208265200","volume":"277","author":"M Zhang","year":"2002","unstructured":"Zhang, M. et al. Osteoblast-specific knockout of the insulin-like growth factor (IGF) receptor gene reveals an essential role of IGF signaling in bone matrix mineralization. J. Biol. Chem. 277, 44005\u201344012 (2002).","journal-title":"J. Biol. Chem."},{"key":"BFnm3583_CR31","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s00774-011-0288-2","volume":"30","author":"A Kyono","year":"2012","unstructured":"Kyono, A., Avishai, N., Ouyang, Z., Landreth, G.E. & Murakami, S. FGF and ERK signaling coordinately regulate mineralization-related genes and play essential roles in osteocyte differentiation. J. Bone Miner. Metab. 30, 19\u201330 (2012).","journal-title":"J. Bone Miner. Metab."},{"key":"BFnm3583_CR32","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1080\/03008200500237203","volume":"46","author":"NE Hatch","year":"2005","unstructured":"Hatch, N.E., Nociti, F., Swanson, E., Bothwell, M. & Somerman, M. FGF2 alters expression of the pyrophosphate\/phosphate regulating proteins, PC-1, ANK and TNAP, in the calvarial osteoblastic cell line, MC3T3E1(C4). Connect. Tissue Res. 46, 184\u2013192 (2005).","journal-title":"Connect. Tissue Res."},{"key":"BFnm3583_CR33","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1359\/jbmr.080220","volume":"23","author":"H Wang","year":"2008","unstructured":"Wang, H. et al. Overexpression of fibroblast growth factor 23 suppresses osteoblast differentiation and matrix mineralization in vitro. J. Bone Miner. Res. 23, 939\u2013948 (2008).","journal-title":"J. Bone Miner. Res."},{"key":"BFnm3583_CR34","doi-asserted-by":"crossref","first-page":"E1636","DOI":"10.1152\/ajpendo.00396.2007","volume":"293","author":"S Liu","year":"2007","unstructured":"Liu, S., Tang, W., Zhou, J., Vierthaler, L. & Quarles, L.D. Distinct roles for intrinsic osteocyte abnormalities and systemic factors in regulation of FGF23 and bone mineralization in Hyp mice. Am. J. Physiol. Endocrinol. Metab. 293, E1636\u2013E1644 (2007).","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"BFnm3583_CR35","doi-asserted-by":"crossref","first-page":"4609","DOI":"10.1038\/sj.onc.1210261","volume":"26","author":"LQ Le","year":"2007","unstructured":"Le, L.Q. & Parada, L.F. Tumor microenvironment and neurofibromatosis type I: connecting the GAPs. Oncogene 26, 4609\u20134616 (2007).","journal-title":"Oncogene"},{"key":"BFnm3583_CR36","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1002\/jbmr.42","volume":"25","author":"W Wang","year":"2010","unstructured":"Wang, W. et al. Local low-dose lovastatin delivery improves the bone-healing defect caused by Nf1 loss of function in osteoblasts. J. Bone Miner. Res. 25, 1658\u20131667 (2010).","journal-title":"J. Bone Miner. Res."},{"key":"BFnm3583_CR37","doi-asserted-by":"crossref","first-page":"3910","DOI":"10.1093\/hmg\/ddr310","volume":"20","author":"W Wang","year":"2011","unstructured":"Wang, W. et al. Mice lacking Nf1 in osteochondroprogenitor cells display skeletal dysplasia similar to patients with neurofibromatosis type I. Hum. Mol. Genet. 20, 3910\u20133924 (2011).","journal-title":"Hum. Mol. Genet."},{"key":"BFnm3583_CR38","doi-asserted-by":"crossref","first-page":"3048","DOI":"10.1093\/hmg\/ddt162","volume":"22","author":"K Ono","year":"2013","unstructured":"Ono, K. et al. The Ras-GTPase activity of neurofibromin restrains ERK-dependent FGFR signaling during endochondral bone formation. Hum. Mol. Genet. 22, 3048\u20133062 (2013).","journal-title":"Hum. Mol. Genet."},{"key":"BFnm3583_CR39","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1002\/(SICI)1097-4644(19971201)67:3<386::AID-JCB10>3.0.CO;2-B","volume":"67","author":"F Lecanda","year":"1997","unstructured":"Lecanda, F., Avioli, L.V. & Cheng, S.L. Regulation of bone matrix protein expression and induction of differentiation of human osteoblasts and human bone marrow stromal cells by bone morphogenetic protein-2. J. Cell. Biochem. 67, 386\u2013396 (1997).","journal-title":"J. Cell. Biochem."},{"key":"BFnm3583_CR40","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/jor.20481","volume":"26","author":"A Schindeler","year":"2008","unstructured":"Schindeler, A. et al. Modeling bone morphogenetic protein and bisphosphonate combination therapy in wild-type and Nf1 haploinsufficient mice. J. Orthop. Res. 26, 65\u201374 (2008).","journal-title":"J. Orthop. Res."},{"key":"BFnm3583_CR41","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1302\/0301-620X.93B8.25940","volume":"93","author":"A Schindeler","year":"2011","unstructured":"Schindeler, A. et al. Distal tibial fracture repair in a neurofibromatosis type 1-deficient mouse treated with recombinant bone morphogenetic protein and a bisphosphonate. J. Bone Joint Surg. Br. 93, 1134\u20131139 (2011).","journal-title":"J. Bone Joint Surg. Br."},{"key":"BFnm3583_CR42","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1056\/NEJMoa1106173","volume":"366","author":"MP Whyte","year":"2012","unstructured":"Whyte, M.P. et al. Enzyme-replacement therapy in life-threatening hypophosphatasia. N. Engl. J. Med. 366, 904\u2013913 (2012).","journal-title":"N. Engl. J. Med."},{"key":"BFnm3583_CR43","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1111\/j.1749-6632.2010.05387.x","volume":"1192","author":"MP Whyte","year":"2010","unstructured":"Whyte, M.P. Physiological role of alkaline phosphatase explored in hypophosphatasia. Ann. NY Acad. Sci. 1192, 190\u2013200 (2010).","journal-title":"Ann. NY Acad. Sci."},{"key":"BFnm3583_CR44","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1002\/jbmr.1619","volume":"27","author":"MC Yadav","year":"2012","unstructured":"Yadav, M.C. et al. Enzyme replacement prevents enamel defects in hypophosphatasia mice. J. Bone Miner. Res. 27, 1722\u20131734 (2012).","journal-title":"J. Bone Miner. Res."},{"key":"BFnm3583_CR45","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.bone.2011.03.770","volume":"49","author":"MC Yadav","year":"2011","unstructured":"Yadav, M.C. et al. Dose response of bone-targeted enzyme replacement for murine hypophosphatasia. Bone 49, 250\u2013256 (2011).","journal-title":"Bone"},{"key":"BFnm3583_CR46","doi-asserted-by":"crossref","first-page":"3231","DOI":"10.1242\/dev.02480","volume":"133","author":"SJ Rodda","year":"2006","unstructured":"Rodda, S.J. & McMahon, A.P. Distinct roles for Hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors. Development 133, 3231\u20133244 (2006).","journal-title":"Development"},{"key":"BFnm3583_CR47","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1101\/gad.862101","volume":"15","author":"Y Zhu","year":"2001","unstructured":"Zhu, Y. et al. Ablation of NF1 function in neurons induces abnormal development of cerebral cortex and reactive gliosis in the brain. Genes Dev. 15, 859\u2013876 (2001).","journal-title":"Genes Dev."},{"key":"BFnm3583_CR48","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1053\/joca.2002.0810","volume":"10","author":"P Sohn","year":"2002","unstructured":"Sohn, P., Crowley, M., Slattery, E. & Serra, R. Developmental and TGF-\u03b2-mediated regulation of Ank mRNA expression in cartilage and bone. Osteoarthritis Cartilage 10, 482\u2013490 (2002).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFnm3583_CR49","doi-asserted-by":"crossref","first-page":"10572","DOI":"10.1074\/jbc.M109.050534","volume":"285","author":"F Cailotto","year":"2010","unstructured":"Cailotto, F., Sebillaud, S., Netter, P., Jouzeau, J.Y. & Bianchi, A. The inorganic pyrophosphate transporter ANK preserves the differentiated phenotype of articular chondrocyte. J. Biol. Chem. 285, 10572\u201310582 (2010).","journal-title":"J. Biol. Chem."},{"key":"BFnm3583_CR50","doi-asserted-by":"crossref","first-page":"634","DOI":"10.2174\/156652409788488801","volume":"9","author":"L Larizza","year":"2009","unstructured":"Larizza, L., Gervasini, C., Natacci, F. & Riva, P. Developmental abnormalities and cancer predisposition in neurofibromatosis type 1. Curr. Mol. Med. 9, 634\u2013653 (2009).","journal-title":"Curr. Mol. Med."},{"key":"BFnm3583_CR51","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1097\/01.bpb.0000194439.75378.ac","volume":"15","author":"D Anticevic","year":"2006","unstructured":"Anticevic, D., Jelic, M. & Vukicevic, S. Treatment of a congenital pseudarthrosis of the tibia by osteogenic protein-1 (bone morphogenetic protein-7): a case report. J. Pediatr. Orthop. B 15, 220\u2013221 (2006).","journal-title":"J. Pediatr. Orthop. B"},{"key":"BFnm3583_CR52","doi-asserted-by":"crossref","first-page":"627","DOI":"10.2106\/00004623-200603000-00023","volume":"88","author":"FY Lee","year":"2006","unstructured":"Lee, F.Y. et al. Treatment of congenital pseudarthrosis of the tibia with recombinant human bone morphogenetic protein-7 (rhBMP-7). A report of five cases. J. Bone Joint Surg. Am. 88, 627\u2013633 (2006).","journal-title":"J. Bone Joint Surg. Am."},{"key":"BFnm3583_CR53","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1302\/0301-620X.88B1.16619","volume":"88","author":"L Fabeck","year":"2006","unstructured":"Fabeck, L., Ghafil, D., Gerroudj, M., Baillon, R. & Delince, P. Bone morphogenetic protein 7 in the treatment of congenital pseudarthrosis of the tibia. J. Bone Joint Surg. Br. 88, 116\u2013118 (2006).","journal-title":"J. Bone Joint Surg. Br."},{"key":"BFnm3583_CR54","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/(SICI)1526-968X(200002)26:2<145::AID-GENE14>3.0.CO;2-C","volume":"26","author":"DA Ovchinnikov","year":"2000","unstructured":"Ovchinnikov, D.A., Deng, J.M., Ogunrinu, G. & Behringer, R.R. Col2a1-directed expression of Cre recombinase in differentiating chondrocytes in transgenic mice. Genesis 26, 145\u2013146 (2000).","journal-title":"Genesis"},{"key":"BFnm3583_CR55","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1359\/jbmr.071213","volume":"23","author":"JL Mill\u00e1n","year":"2008","unstructured":"Mill\u00e1n, J.L. et al. Enzyme replacement therapy for murine hypophosphatasia. J. Bone Miner. Res. 23, 777\u2013787 (2008).","journal-title":"J. Bone Miner. Res."},{"key":"BFnm3583_CR56","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.bone.2009.10.044","volume":"46","author":"D Granchi","year":"2010","unstructured":"Granchi, D. et al. Biological basis for the use of autologous bone marrow stromal cells in the treatment of congenital pseudarthrosis of the tibia. Bone 46, 780\u2013788 (2010).","journal-title":"Bone"},{"key":"BFnm3583_CR57","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1002\/art.1780370624","volume":"37","author":"R Terkeltaub","year":"1994","unstructured":"Terkeltaub, R., Rosenbach, M., Fong, F. & Goding, J. Causal link between nucleotide pyrophosphohydrolase overactivity and increased intracellular inorganic pyrophosphate generation demonstrated by transfection of cultured fibroblasts and osteoblasts with plasma cell membrane glycoprotein-1. Relevance to calcium pyrophosphate dihydrate deposition disease. Arthritis Rheum. 37, 934\u2013941 (1994).","journal-title":"Arthritis Rheum."},{"key":"BFnm3583_CR58","doi-asserted-by":"crossref","first-page":"R122","DOI":"10.1186\/ar2330","volume":"9","author":"F Cailotto","year":"2007","unstructured":"Cailotto, F. et al. Inorganic pyrophosphate generation by transforming growth factor-\u03b2-1 is mainly dependent on ANK induction by Ras\/Raf-1\/extracellular signal-regulated kinase pathways in chondrocytes. Arthritis Res. Ther. 9, R122 (2007).","journal-title":"Arthritis Res. Ther."},{"key":"BFnm3583_CR59","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1002\/jbmr.5650020617","volume":"2","author":"AM Parfitt","year":"1987","unstructured":"Parfitt, A.M. et al. Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J. Bone Miner. Res. 2, 595\u2013610 (1987).","journal-title":"J. Bone Miner. Res."},{"key":"BFnm3583_CR60","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1366\/000370203322554518","volume":"57","author":"CA Lieber","year":"2003","unstructured":"Lieber, C.A. & Mahadevan-Jansen, A. Automated method for subtraction of fluorescence from biological Raman spectra. Appl. Spectrosc. 57, 1363\u20131367 (2003).","journal-title":"Appl. Spectrosc."},{"key":"BFnm3583_CR61","doi-asserted-by":"crossref","first-page":"087012","DOI":"10.1117\/1.3613933","volume":"16","author":"JR Maher","year":"2011","unstructured":"Maher, J.R., Takahata, M., Awad, H.A. & Berger, A.J. Raman spectroscopy detects deterioration in biomechanical properties of bone in a glucocorticoid-treated mouse model of rheumatoid arthritis. J. Biomed. Opt. 16, 087012 (2011).","journal-title":"J. Biomed. Opt."},{"key":"BFnm3583_CR62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bone.2014.01.021","volume":"62","author":"AJ Makowski","year":"2014","unstructured":"Makowski, A.J. et al. The loss of activating transcription factor 4 (ATF4) reduces bone toughness and fracture toughness. Bone 62, 1\u20139 (2014).","journal-title":"Bone"}],"updated-by":[{"DOI":"10.1038\/nm0415-414c","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2015,4,7]],"date-time":"2015-04-07T00:00:00Z","timestamp":1428364800000}}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nm.3583.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm.3583","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm.3583.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T22:46:08Z","timestamp":1684449968000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nm.3583"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,7,6]]},"references-count":62,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2014,8]]}},"alternative-id":["BFnm3583"],"URL":"https:\/\/doi.org\/10.1038\/nm.3583","relation":{"erratum":[{"id-type":"doi","id":"10.1038\/nm0415-414c","asserted-by":"object"}]},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,7,6]]},"assertion":[{"value":"12 December 2013","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 May 2014","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 July 2014","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 March 2015","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Corrigendum","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"\u00a0In the version of this article initially published, the acknowledgment that Daniel S. Perrien was supported by a Career Development Award from the US Department of Veterans Affairs was omitted. The error has been corrected in the HTML and PDF versions of the article.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"D.A.S. has received honoraria from Alexion for consultation on hypophosphatasia.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}