{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:34:37Z","timestamp":1788435277371,"version":"build-2803163510"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"16","license":[{"start":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T00:00:00Z","timestamp":1594252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Deutsche Muskelstiftung"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Spinal muscular atrophy (SMA) is a fatal neurodegenerative disease of newborns and children caused by mutations or deletions of the survival of motoneuron gene 1 resulting in low levels of the SMN protein. While neuromuscular degeneration is the cardinal symptom of the disease, the reduction of the ubiquitously expressed SMN additionally elicits non-motoneuron symptoms. Impaired bone development is a key feature of SMA, but it is yet unknown whether this is an indirect functional consequence of muscle weakness or caused by bone-intrinsic mechanisms. Therefore, we radiologically examined SMA patients in a prospective, non-randomized cohort study characterizing bone size and bone mineral density (BMD) and performed equivalent measurements in pre-symptomatic SMA mice. BMD as well as lumbar vertebral body size were significantly reduced in SMA patients. This growth defect but not BMD reduction was confirmed in SMA mice by \u03bcCT before the onset of neuromuscular symptoms indicating that it is at least partially independent of neuromuscular degeneration. Interestingly, the number of chondroblasts in the hypertrophic zone of the growth plate was significantly reduced. This was underlined by RNAseq and expression data from developing SMA mice vertebral bodies, which revealed molecular changes related to cell division and cartilage remodeling. Together, these findings suggest a bone intrinsic defect in SMA. This phenotype may not be rescued by novel drugs that enhance SMN levels in the central nervous system only.<\/jats:p>","DOI":"10.1093\/hmg\/ddaa145","type":"journal-article","created":{"date-parts":[[2020,7,7]],"date-time":"2020-07-07T15:09:53Z","timestamp":1594134593000},"page":"2662-2673","source":"Crossref","is-referenced-by-count":34,"title":["Altered bone development with impaired cartilage formation precedes neuromuscular symptoms in spinal muscular atrophy"],"prefix":"10.1093","volume":"29","author":[{"given":"Niko","family":"Hensel","sequence":"first","affiliation":[{"name":"Institute of Neuroanatomy and Cell Biology, Hannover Medical School, Hannover, Germany"},{"name":"Center for Systems Neurosciences (ZSN), Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Brickwedde","sequence":"additional","affiliation":[{"name":"Institute of Neuroanatomy and Cell Biology, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Tsaknakis","sequence":"additional","affiliation":[{"name":"Pediatric Orthopedics, Department of Trauma, Orthopedic and Plastic Surgery, University Medical Center Goettingen, Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Grages","sequence":"additional","affiliation":[{"name":"Pediatric Orthopedics, Department of Trauma, Orthopedic and Plastic Surgery, University Medical Center Goettingen, Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Braunschweig","sequence":"additional","affiliation":[{"name":"Pediatric Orthopedics, Department of Trauma, Orthopedic and Plastic Surgery, University Medical Center Goettingen, Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja A","family":"L\u00fcders","sequence":"additional","affiliation":[{"name":"Pediatric Orthopedics, Department of Trauma, Orthopedic and Plastic Surgery, University Medical Center Goettingen, Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiko M","family":"Lorenz","sequence":"additional","affiliation":[{"name":"Pediatric Orthopedics, Department of Trauma, Orthopedic and Plastic Surgery, University Medical Center Goettingen, Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Lippross","sequence":"additional","affiliation":[{"name":"Pediatric Orthopedics, Department of Trauma, Orthopedic and Plastic Surgery, University Medical Center Goettingen, Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M","family":"Walter","sequence":"additional","affiliation":[{"name":"Institute of Neuroanatomy and Cell Biology, Hannover Medical School, Hannover, Germany"},{"name":"Center for Systems Neurosciences (ZSN), Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Tavassol","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Lienenklaus","sequence":"additional","affiliation":[{"name":"Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Neunaber","sequence":"additional","affiliation":[{"name":"Trauma Department, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Claus","sequence":"additional","affiliation":[{"name":"Institute of Neuroanatomy and Cell Biology, Hannover Medical School, Hannover, Germany"},{"name":"Center for Systems Neurosciences (ZSN), Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna K","family":"Hell","sequence":"additional","affiliation":[{"name":"Pediatric Orthopedics, Department of Trauma, Orthopedic and Plastic Surgery, University Medical Center Goettingen, Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,7,9]]},"reference":[{"key":"2020110419222825600_ref1","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/344540a0","article-title":"Genetic mapping of chronic childhood-onset spinal muscular atrophy to chromosome 5q11.2-13.3","volume":"344","author":"Brzustowicz","year":"1990","journal-title":"Nature"},{"key":"2020110419222825600_ref2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0092-8674(95)90460-3","article-title":"Identification and characterization of a spinal muscular atrophy-determining 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Mol. Genet."},{"key":"2020110419222825600_ref4","doi-asserted-by":"crossref","first-page":"6307","DOI":"10.1073\/pnas.96.11.6307","article-title":"A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy","volume":"96","author":"Lorson","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2020110419222825600_ref5","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1086\/513886","article-title":"Genomic variation and gene conversion in spinal muscular atrophy: implications for disease process and clinical phenotype","volume":"61","author":"Campbell","year":"1997","journal-title":"Am. J. Hum. Genet."},{"key":"2020110419222825600_ref6","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/S0960-8966(06)80015-5","article-title":"International SMA consortium meeting. (26-28 June 1992, Bonn, Germany)","volume":"2","author":"Munsat","year":"1992","journal-title":"Neuromuscul. Disord."},{"key":"2020110419222825600_ref7","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.nmd.2015.04.009","article-title":"209th ENMC international workshop: outcome measures and clinical trial readiness in spinal muscular atrophy 7-9 November 2014, Heemskerk, the Netherlands","volume":"25","author":"Finkel","year":"2015","journal-title":"Neuromuscul. Disord."},{"key":"2020110419222825600_ref8","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1177\/0883073807305788","article-title":"Consensus statement for standard of care in spinal muscular atrophy","volume":"22","author":"Wang","year":"2007","journal-title":"J. Child Neurol."},{"key":"2020110419222825600_ref9","doi-asserted-by":"crossref","first-page":"487","DOI":"10.3233\/JND-160177","article-title":"Type 0 spinal muscular atrophy: further delineation of prenatal and postnatal features in 16 patients","volume":"3","author":"Grotto","year":"2016","journal-title":"J. Neuromuscul. 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Pediatr."},{"key":"2020110419222825600_ref14","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/ana.24549","article-title":"Vascular defects and spinal cord hypoxia in spinal muscular atrophy","volume":"79","author":"Somers","year":"2016","journal-title":"Ann. Neurol."},{"key":"2020110419222825600_ref15","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1002\/mus.21654","article-title":"Digital necroses and vascular thrombosis in severe spinal muscular atrophy","volume":"42","author":"Rudnik-Schoneborn","year":"2010","journal-title":"Muscle Nerve"},{"key":"2020110419222825600_ref16","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1038\/labinvest.3700163","article-title":"Reduced expression of nicotinic AChRs in myotubes from spinal muscular atrophy I patients","volume":"84","author":"Arnold","year":"2004","journal-title":"Lab. 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Mech."},{"key":"2020110419222825600_ref23","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.nmd.2017.01.019","article-title":"Low bone mineral density and fractures are highly prevalent in pediatric patients with spinal muscular atrophy regardless of disease severity","volume":"27","author":"Wasserman","year":"2017","journal-title":"Neuromuscul. Disord."},{"key":"2020110419222825600_ref24","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1097\/CND.0b013e318183e0fa","article-title":"Low bone mineral density in spinal muscular atrophy","volume":"10","author":"Khatri","year":"2008","journal-title":"J. Clin. Neuromuscul. 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Virol."},{"key":"2020110419222825600_ref30","doi-asserted-by":"crossref","first-page":"45","DOI":"10.3389\/fneur.2020.00045","article-title":"The need for SMN-independent treatments of spinal muscular atrophy (SMA) to complement SMN-enhancing drugs","volume":"11","author":"Hensel","year":"2020","journal-title":"Front. Neurol."},{"key":"2020110419222825600_ref31","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1148\/radiology.166.3.3340782","article-title":"Vertebral bone density in children: effect of puberty","volume":"166","author":"Gilsanz","year":"1988","journal-title":"Radiology"},{"key":"2020110419222825600_ref32","first-page":"380","article-title":"Quantitative spinal mineral analysis in children","volume":"29","author":"Gilsanz","year":"1986","journal-title":"Ann. Radiol. (Paris)"},{"key":"2020110419222825600_ref33","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/71709","article-title":"A mouse model for spinal muscular atrophy","volume":"24","author":"Hsieh-Li","year":"2000","journal-title":"Nat. Genet."},{"key":"2020110419222825600_ref34","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.nbd.2017.09.005","article-title":"ERK and ROCK functionally interact in a signaling network that is compensationally upregulated in spinal muscular atrophy","volume":"108","author":"Hensel","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"2020110419222825600_ref35","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/S8756-3282(96)00217-7","article-title":"Distribution of platelet-derived growth factor (PDGF) a chain mRNA, protein, and PDGF-alpha receptor in rapidly forming human bone","volume":"19","author":"Horner","year":"1996","journal-title":"Bone"},{"key":"2020110419222825600_ref36","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1242\/jcs.113.1.59","article-title":"Vascular endothelial growth factor (VEGF) in cartilage neovascularization and chondrocyte differentiation: auto-paracrine role during endochondral bone formation","volume":"113","author":"Carlevaro","year":"2000","journal-title":"J. Cell Sci."},{"key":"2020110419222825600_ref37","first-page":"33","article-title":"Evaluation of the changes in the bone structures of the human axial skeleton in prolonged space flight","volume":"18","author":"Stupakov","year":"1984","journal-title":"Kosm. Biol. Aviakosm. Med."},{"key":"2020110419222825600_ref38","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/0094-5765(95)00131-X","article-title":"Bone and body mass changes during space flight","volume":"36","author":"Schneider","year":"1995","journal-title":"Acta Astronaut."},{"key":"2020110419222825600_ref39","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1097\/BSD.0000000000000614","article-title":"Combining bilateral magnetically controlled implants inserted parallel to the spine with rib to pelvis fixation: surgical technique and early results","volume":"31","author":"Hell","year":"2018","journal-title":"Clin. Spine Surg."},{"key":"2020110419222825600_ref40","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/path.2566","article-title":"Bone loss in survival motor neuron (SMN(\u2212\/\u2212) SMN2) genetic mouse model of spinal muscular atrophy","volume":"219","author":"Shanmugarajan","year":"2009","journal-title":"J. Pathol."},{"key":"2020110419222825600_ref41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mbs.2019.04.005","article-title":"Growth of a long bone cross section - a 2D phase-field model","volume":"313","author":"Lindberg","year":"2019","journal-title":"Math. Biosci."},{"key":"2020110419222825600_ref42","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/bs.ctdb.2018.11.003","article-title":"ECM signaling in cartilage development and endochondral ossification","volume":"133","author":"Prein","year":"2019","journal-title":"Curr. Top. Dev. Biol."},{"key":"2020110419222825600_ref43","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.bbrc.2012.02.127","article-title":"ROCK inhibitor prevents the dedifferentiation of human articular chondrocytes","volume":"420","author":"Matsumoto","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2020110419222825600_ref44","doi-asserted-by":"crossref","first-page":"4262","DOI":"10.1128\/MCB.01779-08","article-title":"The transcriptional activity of Sox9 in chondrocytes is regulated by RhoA signaling and actin polymerization","volume":"29","author":"Kumar","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"2020110419222825600_ref45","doi-asserted-by":"crossref","first-page":"13205","DOI":"10.1074\/jbc.M311427200","article-title":"RhoA\/ROCK signaling suppresses hypertrophic chondrocyte differentiation","volume":"279","author":"Wang","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2020110419222825600_ref46","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1359\/JBMR.050113","article-title":"Rac1\/Cdc42 and RhoA GTPases antagonistically regulate chondrocyte proliferation, hypertrophy, and apoptosis","volume":"20","author":"Wang","year":"2005","journal-title":"J. Bone Miner. Res."},{"key":"2020110419222825600_ref47","doi-asserted-by":"crossref","first-page":"4865","DOI":"10.1093\/hmg\/ddr425","article-title":"The spinal muscular atrophy disease protein SMN is linked to the rho-kinase pathway via profilin","volume":"20","author":"Nolle","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"2020110419222825600_ref48","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1093\/hmg\/ddq021","article-title":"Rho-kinase inactivation prolongs survival of an intermediate SMA mouse model","volume":"19","author":"Bowerman","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"2020110419222825600_ref49","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.cellsig.2013.11.027","article-title":"Bilateral crosstalk of rho- and extracellular-signal-regulated-kinase (ERK) pathways is confined to an unidirectional mode in spinal muscular atrophy (SMA)","volume":"26","author":"Hensel","year":"2014","journal-title":"Cell. 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Cell Biol."},{"key":"2020110419222825600_ref53","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1093\/brain\/awz373","article-title":"ZPR1 prevents R-loop accumulation, upregulates SMN2 expression and rescues spinal muscular atrophy","volume":"143","author":"Kannan","year":"2020","journal-title":"Brain"},{"key":"2020110419222825600_ref54","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1359\/jbmr.2001.16.11.2005","article-title":"Developmental distribution of collagen type XII in cartilage: association with articular cartilage and the growth plate","volume":"16","author":"Gregory","year":"2001","journal-title":"J. Bone Miner. Res."},{"key":"2020110419222825600_ref55","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.ceb.2008.06.008","article-title":"Collagen fibrillogenesis: fibronectin, integrins, and minor collagens as organizers and nucleators","volume":"20","author":"Kadler","year":"2008","journal-title":"Curr. Opin. Cell Biol."},{"key":"2020110419222825600_ref56","doi-asserted-by":"crossref","first-page":"2744","DOI":"10.1128\/MCB.25.7.2744-2756.2005","article-title":"ZPR1 is essential for survival and is required for localization of the survival motor neurons (SMN) protein to Cajal bodies","volume":"25","author":"Gangwani","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"2020110419222825600_ref57","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/ajmg.c.31552","article-title":"The 2017 international classification of the Ehlers-Danlos syndromes","volume":"175","author":"Malfait","year":"2017","journal-title":"Am. J. Med. Genet. C Semin. Med. Genet."},{"key":"2020110419222825600_ref58","first-page":"113","article-title":"Proximal spinal muscular atrophy: current orthopedic perspective","volume":"6","author":"Haaker","year":"2013","journal-title":"Appl. Clin. 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Genet."},{"key":"2020110419222825600_ref65","doi-asserted-by":"crossref","first-page":"e31202","DOI":"10.1371\/journal.pone.0031202","article-title":"Analysis of the fibroblast growth factor system reveals alterations in a mouse model of spinal muscular atrophy","volume":"7","author":"Hensel","year":"2012","journal-title":"PLoS One"},{"key":"2020110419222825600_ref66","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1002\/jbmr.5650020617","article-title":"Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry nomenclature committee","volume":"2","author":"Parfitt","year":"1987","journal-title":"J. Bone Miner. 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