{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T20:42:06Z","timestamp":1783716126485,"version":"3.55.0"},"reference-count":78,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Plastin-3 (PLS3) is a calcium-sensitive actin-bundling protein that has recently been linked to the development of childhood-onset osteoporosis. Clinical data suggest that PLS3 mutations lead to a defect in osteoblast function, however the underlying mechanism remains elusive. To investigate the role of PLS3 in bone mineralization, we generated MC3T3-E1 preosteoblast cells that are stably depleted of PLS3. Analysis of osteogenic differentiation of control and PLS3 knockdown (PLS3 KD) cells showed that depletion of PLS3 does not alter the first stage of osteoblast mineralization in which a collagen matrix is deposited, but severely affects the subsequent mineralization of that matrix. During this phase, osteoblasts heavily rely on mechanosensitive signaling pathways to sustain mineral deposition in response to increasing stiffness of the extracellular matrix (ECM). PLS3 prominently localizes to focal adhesions (FAs), which are intricately linked to mechanosensation. In line with this, we observed that depletion of PLS3 rendered osteoblasts unresponsive to changes in ECM stiffness and showed the same cell size, FA lengths and number of FAs when plated on soft (6\u00a0kPa) <jats:italic>versus<\/jats:italic> stiff (100\u00a0kPa) substrates in contrast to control cells, which showed an increased in each of these parameters when plated on 100\u00a0kPa substrates. Defective cell spreading of PLS3 KD cells on stiff substrates could be rescued by expression of wildtype PLS3, but not by expression of three PLS3 mutations that were identified in patients with early onset osteoporosis and that have aberrant actin-bundling activity. Altogether, our results show that actin-bundling by PLS3 is part of the mechanosensitive mechanism that promotes osteoblast mineralization and thus begins to elucidate how PLS3 contributes to the development of bone defects such as osteoporosis.<\/jats:p>","DOI":"10.3389\/fcell.2023.1141738","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T06:38:31Z","timestamp":1701067111000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["The actin-bundling protein, PLS3, is part of the mechanoresponsive machinery that regulates osteoblast mineralization"],"prefix":"10.3389","volume":"11","author":[{"given":"Samantha M.","family":"Chin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela","family":"Unnold-Cofre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teri","family":"Naismith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Jansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.bone.2014.11.003","article-title":"Extracellular matrix mineralization in murine MC3T3-E1 osteoblast cultures: an ultrastructural, compositional and comparative analysis with mouse bone","volume":"71","author":"Addison","year":"2015","journal-title":"Bone"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1002\/ajmg.a.38830","article-title":"Novel PLS3 variants in X-linked osteoporosis: exploring bone material properties","volume":"176","author":"Balasubramanian","year":"2018","journal-title":"Am. J. Med. Genet. Part A"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2999","DOI":"10.1007\/s00018-017-2511-3","article-title":"Vinculin in cell-cell and cell-matrix adhesions","volume":"74","author":"Bays","year":"2017","journal-title":"Cell. Mol. life Sci. CMLS"},{"key":"B4","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1089\/ten.teb.2016.0454","article-title":"Osteoblast differentiation and bone matrix formation in vivo and in vitro","volume":"23","author":"Blair","year":"2017","journal-title":"Tissue Eng. Part B Rev."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1835","DOI":"10.1007\/s00198-010-1419-7","article-title":"Medical costs of osteoporosis in the elderly Medicare population","volume":"22","author":"Blume","year":"2011","journal-title":"Osteoporos. Int."},{"key":"B6","doi-asserted-by":"publisher","first-page":"e104700","DOI":"10.1371\/journal.pone.0104700","article-title":"T-plastin expression downstream to the calcineurin\/NFAT pathway is involved in keratinocyte migration","volume":"9","author":"Brun","year":"2014","journal-title":"PLoS ONE"},{"key":"B7","first-page":"27","article-title":"Bone structure and function","volume":"36","author":"Buckwalter","year":"1987","journal-title":"Instr. Course Lect."},{"key":"B8","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.abb.2014.05.003","article-title":"Osteoblast and osteocyte: games without frontiers","volume":"561","author":"Capulli","year":"2014","journal-title":"Archives Biochem. Biophysics"},{"key":"B9","first-page":"297","article-title":"Structure-function relationships in the stem cell\u2019s mechanical world B: emergent anisotropy of the cytoskeleton correlates to volume and shape changing stress exposure","volume":"8","author":"Chang","year":"2011","journal-title":"Mol. Cell. biomechanics MCB"},{"key":"B10","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.scr.2015.06.009","article-title":"Inhibiting actin depolymerization enhances osteoblast differentiation and bone formation in human stromal stem cells","volume":"15","author":"Chen","year":"2015","journal-title":"Stem Cell Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.tcb.2007.02.002","article-title":"Myosin II and mechanotransduction: a balancing act","volume":"17","author":"Clark","year":"2007","journal-title":"Trends Cell Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1038\/s10038-018-0472-5","article-title":"A novel frameshift deletion in PLS3 causing severe primary osteoporosis","volume":"63","author":"Costantini","year":"2018","journal-title":"J. Hum. Genet."},{"key":"B13","doi-asserted-by":"publisher","first-page":"187","DOI":"10.7861\/clinmedicine.14-2-187","article-title":"Osteoporosis and fracture risk in older people","volume":"14","author":"Coughlan","year":"2014","journal-title":"Clin. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2087","DOI":"10.1002\/jbmr.3190","article-title":"Integrin-linked kinase regulates bone formation by controlling cytoskeletal organization and modulating BMP and wnt signaling in osteoprogenitors","volume":"32","author":"Dejaeger","year":"2017","journal-title":"J. Bone Mineral Res. Official J. Am. Soc. Bone Mineral Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1111\/j.1745-7254.2005.00145.x","article-title":"Plastins: versatile modulators of actin organization in (patho)physiological cellular processes","volume":"26","author":"Delanote","year":"2005","journal-title":"Acta Pharmacol. Sin."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1083\/jcb.201603070","article-title":"Plastin increases cortical connectivity to facilitate robust polarization and timely cytokinesis","volume":"216","author":"Ding","year":"2017","journal-title":"J. Cell Biol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1002\/bdrc.21047","article-title":"Osteoblast recruitment to sites of bone formation in skeletal development, homeostasis, and regeneration","volume":"99","author":"Dirckx","year":"2013","journal-title":"Birth Defects Res. Part C, Embryo Today Rev."},{"key":"B18","doi-asserted-by":"publisher","first-page":"eaal3154","DOI":"10.1126\/scisignal.aal3154","article-title":"T-plastin is essential for basement membrane assembly and epidermal morphogenesis","volume":"10","author":"Dor-On","year":"2017","journal-title":"Sci. Signal."},{"key":"B19","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/j.cell.2006.06.044","article-title":"Matrix elasticity directs stem cell lineage specification","volume":"126","author":"Engler","year":"2006","journal-title":"Cell"},{"key":"B20","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1038\/s41467-022-28319-3","article-title":"ROCK1 mechano-signaling dependency of human malignancies driven by TEAD\/YAP activation","volume":"13","author":"Esposito","year":"2022","journal-title":"Nat. Commun."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1805","DOI":"10.1002\/jbmr.2208","article-title":"Osteoporosis caused by mutations in PLS3: clinical and bone tissue characteristics: PLS3 mutations and osteoporosis","volume":"29","author":"Fahiminiya","year":"2014","journal-title":"J. Bone Mineral Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1038\/nature08908","article-title":"Cell mechanics and the cytoskeleton","volume":"463","author":"Fletcher","year":"2010","journal-title":"Nature"},{"key":"B23","doi-asserted-by":"publisher","first-page":"421746","DOI":"10.1155\/2015\/421746","article-title":"Biology of bone tissue: structure, function, and factors that influence bone cells","volume":"2015","author":"Florencio-Silva","year":"2015","journal-title":"BioMed Res. Int."},{"key":"B24","doi-asserted-by":"publisher","first-page":"4818","DOI":"10.1038\/s41467-020-18586-3","article-title":"T-Plastin reinforces membrane protrusions to bridge matrix gaps during cell migration","volume":"11","author":"Garbett","year":"2020","journal-title":"Nat. Commun."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/BF00140319","article-title":"Vinculin, talin and focal adhesions","volume":"17","author":"Goldmann","year":"1996","journal-title":"J. Muscle Res. Cell Motil."},{"key":"B26","doi-asserted-by":"publisher","first-page":"115971","DOI":"10.1016\/j.bone.2021.115971","article-title":"The cytoskeleton and connected elements in bone cell mechano-transduction","volume":"149","author":"Gould","year":"2021","journal-title":"Bone"},{"key":"B27","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1016\/j.bbrc.2011.03.082","article-title":"Interaction of activated Rab5 with actin-bundling proteins, L- and T-plastin and its relevance to endocytic functions in mammalian cells","volume":"407","author":"Hagiwara","year":"2011","journal-title":"Biochem. Biophysical Res. Commun."},{"key":"B28","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1091\/mbc.E18-06-0345","article-title":"Actomyosin contractility modulates Wnt signaling through adherens junction stability","volume":"30","author":"Hall","year":"2019","journal-title":"Mol. Biol. Cell"},{"key":"B29","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.mex.2014.06.004","article-title":"Step-by-step quantitative analysis of focal adhesions","volume":"1","author":"Horzum","year":"2014","journal-title":"MethodsX"},{"key":"B30","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1359\/JBMR.040128","article-title":"Terminal differentiation of osteoblasts to osteocytes is accompanied by dramatic changes in the distribution of actin-binding proteins","volume":"19","author":"Kamioka","year":"2004","journal-title":"J. Bone Mineral Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"3023","DOI":"10.1007\/s00198-017-4150-9","article-title":"PLS3 sequencing in childhood-onset primary osteoporosis identifies two novel disease-causing variants","volume":"28","author":"K\u00e4mpe","year":"","journal-title":"Osteoporos. Int."},{"key":"B32","doi-asserted-by":"publisher","first-page":"2394","DOI":"10.1002\/jbmr.3233","article-title":"PLS3 deletions lead to severe spinal osteoporosis and disturbed bone matrix mineralization: PLS3 DELETIONS LEAD TO SEVERE SPINAL OSTEOPOROSIS","volume":"32","author":"K\u00e4mpe","year":"","journal-title":"J. Bone Mineral Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1159\/000477242","article-title":"PLS3 mutations in X-linked osteoporosis: clinical and bone characteristics of two novel mutations","volume":"88","author":"Kannu","year":"2017","journal-title":"Hormone Res. Paediatr."},{"key":"B34","doi-asserted-by":"publisher","first-page":"4305","DOI":"10.1016\/j.actbio.2010.06.001","article-title":"Substrate stiffness and contractile behaviour modulate the functional maturation of osteoblasts on a collagen-GAG scaffold","volume":"6","author":"Keogh","year":"2010","journal-title":"Acta Biomater."},{"key":"B35","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1186\/s13287-020-01789-2","article-title":"A glance on the role of actin in osteogenic and adipogenic differentiation of mesenchymal stem cells","volume":"11","author":"Khan","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"B36","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1007\/978-1-4939-9030-6_16","article-title":"Characterization of the EF-hand calcium-binding domains of human plastins","volume":"1929","author":"Khassan","year":"2019","journal-title":"Methods Mol. Biol. Clift. N.J.)"},{"key":"B37","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1016\/S2213-8587(17)30188-2","article-title":"Osteoporosis treatment: recent developments and ongoing challenges","volume":"5","author":"Khosla","year":"2017","journal-title":"Lancet Diabetes & Endocrinol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1002\/stem.1860","article-title":"Oscillatory shear stress mediates directional reorganization of actin cytoskeleton and alters differentiation propensity of mesenchymal stem cells","volume":"33","author":"Kuo","year":"2015","journal-title":"Stem Cells Dayt. Ohio)"},{"key":"B39","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1002\/jbmr.2355","article-title":"A novel splice mutation in PLS3 causes X-linked early onset low-turnover osteoporosis: PLS3 mutation and EARLY-ONSET osteoporosis","volume":"30","author":"Laine","year":"2015","journal-title":"J. Bone Mineral Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"e390","DOI":"10.1371\/journal.pone.0000390","article-title":"FAK-mediated mechanotransduction in skeletal regeneration","volume":"2","author":"Leucht","year":"2007","journal-title":"PLoS ONE"},{"key":"B41","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1038\/nature13701","article-title":"Piezo1 integration of vascular architecture with physiological force","volume":"515","author":"Li","year":"2014","journal-title":"Nature"},{"key":"B42","doi-asserted-by":"publisher","first-page":"2781","DOI":"10.1016\/S0021-9258(18)53842-4","article-title":"Human plastin genes. Comparative gene structure, chromosome location, and differential expression in normal and neoplastic cells","volume":"268","author":"Lin","year":"1993","journal-title":"J. Biol. Chem."},{"key":"B43","doi-asserted-by":"publisher","first-page":"8722","DOI":"10.1073\/pnas.1704460114","article-title":"Atypical fracture with long-term bisphosphonate therapy is associated with altered cortical composition and reduced fracture resistance","volume":"114","author":"Lloyd","year":"2017","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1002\/jbmr.3409","article-title":"Live imaging of type I collagen assembly dynamics in osteoblasts stably expressing GFP and mCherry-tagged collagen constructs: LIVE imaging of type I collagen assembly","volume":"33","author":"Lu","year":"2018","journal-title":"J. Bone Mineral Res."},{"key":"B45","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/s41413-022-00223-y","article-title":"Biomechanics and mechanobiology of the bone matrix","volume":"10","author":"Ma","year":"2022","journal-title":"Bone Res."},{"key":"B46","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1007\/s00223-021-00885-6","article-title":"Early-onset osteoporosis","volume":"110","author":"M\u00e4kitie","year":"2022","journal-title":"Calcif. Tissue Int."},{"key":"B47","doi-asserted-by":"publisher","first-page":"824","DOI":"10.3389\/fphys.2018.00824","article-title":"Cellular mechanotransduction: from tension to function","volume":"9","author":"Martino","year":"2018","journal-title":"Front. Physiology"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.1016\/j.bpj.2015.02.022","article-title":"The effect of substrate stiffness, thickness, and cross-linking density on osteogenic cell behavior","volume":"108","author":"Mullen","year":"2015","journal-title":"Biophysical J."},{"key":"B49","doi-asserted-by":"publisher","first-page":"20140885","DOI":"10.1098\/rsif.2014.0885","article-title":"Cell morphology and focal adhesion location alters internal cell stress","volume":"11","author":"Mullen","year":"2014","journal-title":"J. R. Soc. Interface"},{"key":"B50","doi-asserted-by":"publisher","first-page":"4249","DOI":"10.1093\/hmg\/ddy318","article-title":"\u2018Plastin 3 influences bone homeostasis through regulation of osteoclast activity","volume":"27","author":"Neugebauer","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"B51","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1093\/jb\/mvw082","article-title":"Roles of the cytoskeleton, cell adhesion and rho signalling in mechanosensing and mechanotransduction","volume":"161","author":"Ohashi","year":"2017","journal-title":"J. Biochem."},{"key":"B52","doi-asserted-by":"publisher","first-page":"e0170312","DOI":"10.1371\/journal.pone.0170312","article-title":"Substrate stiffness controls osteoblastic and chondrocytic differentiation of mesenchymal stem cells without exogenous stimuli","volume":"12","author":"Olivares-Navarrete","year":"2017","journal-title":"PloS One"},{"key":"B53","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1161\/ATVBAHA.119.313440","article-title":"S-nitrosylation of plastin-3 exacerbates thoracic aortic dissection formation via endothelial barrier dysfunction","volume":"40","author":"Pan","year":"2020","journal-title":"Arteriosclerosis, Thrombosis, Vasc. Biol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/j.cub.2008.02.056","article-title":"Interactions between Myosin and actin crosslinkers control cytokinesis contractility dynamics and mechanics","volume":"18","author":"Reichl","year":"2008","journal-title":"Curr. Biol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"95","DOI":"10.12659\/MSMBR.901142","article-title":"Osteoblast differentiation at a glance","volume":"22","author":"Rutkovskiy","year":"2016","journal-title":"Med. Sci. Monit. Basic Res."},{"key":"B56","doi-asserted-by":"publisher","first-page":"644595","DOI":"10.3389\/fbioe.2021.644595","article-title":"Mimicking the hierarchical organization of natural collagen: toward the development of ideal scaffolding material for tissue regeneration","volume":"9","author":"Salvatore","year":"2021","journal-title":"Front. Bioeng. Biotechnol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"2490","DOI":"10.1016\/j.jmb.2017.06.021","article-title":"The roles of actin-binding domains 1 and 2 in the calcium-dependent regulation of actin filament bundling by human plastins","volume":"429","author":"Schwebach","year":"2017","journal-title":"J. Mol. Biol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/s41413-020-0095-2","article-title":"Osteogenesis imperfecta mutations in plastin 3 lead to impaired calcium regulation of actin bundling","volume":"8","author":"Schwebach","year":"2020","journal-title":"Bone Res."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1038\/s41401-019-0219-7","article-title":"Genetic variants in the PLS3 gene are associated with osteoporotic fractures in postmenopausal Chinese women","volume":"40","author":"Shao","year":"2019","journal-title":"Acta Pharmacol. Sin."},{"key":"B60","doi-asserted-by":"publisher","first-page":"178","DOI":"10.3389\/fcell.2019.00178","article-title":"Collagen dynamics during the process of osteocyte embedding and mineralization","volume":"7","author":"Shiflett","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.bbrc.2019.04.093","article-title":"Regulation of MC3T3-E1 differentiation by actin cytoskeleton through lipid mediators reflecting the cell differentiation stage","volume":"514","author":"Suzuki","year":"2019","journal-title":"Biochem. Biophysical Res. Commun."},{"key":"B62","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1007\/s10439-005-3555-3","article-title":"Osteoblast elastic modulus measured by atomic force microscopy is substrate dependent","volume":"33","author":"Takai","year":"2005","journal-title":"Ann. Biomed. Eng."},{"key":"B63","doi-asserted-by":"publisher","first-page":"Unit 10.16","DOI":"10.1002\/0471143030.cb1016s47","article-title":"Preparation of hydrogel substrates with tunable mechanical properties","volume":"47","author":"Tse","year":"2010","journal-title":"Curr. Protoc. Cell Biol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1007\/s11914-017-0373-0","article-title":"Osteocyte mechanobiology","volume":"15","author":"Uda","year":"2017","journal-title":"Curr. Osteoporos. Rep."},{"key":"B65","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1056\/NEJMoa1308223","article-title":"PLS3 mutations in X-linked osteoporosis with fractures","volume":"369","author":"van Dijk","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"B66","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1111\/ahg.12344","article-title":"A novel nonsense variant in PLS3 causes X-linked osteoporosis in a Chinese family","volume":"84","author":"Wang","year":"2020","journal-title":"Ann. Hum. Genet."},{"key":"B67","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1111\/cge.13081","article-title":"Functional analysis of p.Ala253_Leu254insAsn mutation in PLS3 responsible for X-linked osteoporosis: WANG et al","volume":"93","author":"Wang","year":"2018","journal-title":"Clin. Genet."},{"key":"B68","doi-asserted-by":"publisher","first-page":"131692","DOI":"10.1172\/jci.insight.131692","article-title":"Focal adhesion proteins Pinch1 and Pinch2 regulate bone homeostasis in mice","volume":"4","author":"Wang","year":"2019","journal-title":"JCI insight"},{"key":"B69","doi-asserted-by":"publisher","first-page":"2147","DOI":"10.1007\/s00198-016-3515-9","article-title":"The management of osteoporosis in children","volume":"27","author":"Ward","year":"2016","journal-title":"Osteoporos. Int."},{"key":"B70","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1007\/s00198-015-3440-3","article-title":"The National Osteoporosis Foundations position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations","volume":"27","author":"Weaver","year":"2016","journal-title":"Osteoporos. Int."},{"key":"B71","doi-asserted-by":"publisher","first-page":"2340","DOI":"10.1210\/jc.2017-00099","article-title":"Osteocyte protein expression is altered in low-turnover osteoporosis caused by mutations in WNT1 and PLS3","volume":"102","author":"Wesseling-Perry","year":"2017","journal-title":"J. Clin. Endocrinol. Metabolism"},{"key":"B72","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1111\/apha.12859","article-title":"Hypoxia-stimulated membrane trafficking requires T-plastin","volume":"221","author":"Wottawa","year":"2017","journal-title":"Acta Physiol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"4453","DOI":"10.1074\/jbc.275.6.4453","article-title":"MAPK pathways activate and phosphorylate the osteoblast-specific transcription factor, Cbfa1","volume":"275","author":"Xiao","year":"2000","journal-title":"J. Biol. Chem."},{"key":"B74","doi-asserted-by":"publisher","first-page":"115062","DOI":"10.1016\/j.bone.2019.115062","article-title":"Mice lacking plastin-3 display a specific defect of cortical bone acquisition","volume":"130","author":"Yorgan","year":"2020","journal-title":"Bone"},{"key":"B75","doi-asserted-by":"publisher","first-page":"2209","DOI":"10.1242\/jcs.170068","article-title":"The contractome \u2013 a systems view of actomyosin contractility in non-muscle cells","volume":"128","author":"Zaidel-Bar","year":"2015","journal-title":"J. Cell Sci."},{"key":"B76","doi-asserted-by":"publisher","first-page":"4025083","DOI":"10.1155\/2018\/4025083","article-title":"Osteogenesis-related behavior of mc3t3-E1 cells on substrates with tunable stiffness","volume":"2018","author":"Zhang","year":"2018","journal-title":"BioMed Res. Int."},{"key":"B77","doi-asserted-by":"publisher","first-page":"312","DOI":"10.12336\/biomatertransl.2021.04.007","article-title":"Focal adhesion regulates osteogenic differentiation of mesenchymal stem cells and osteoblasts","volume":"2","author":"Zhao","year":"2021","journal-title":"Biomater. Transl."},{"key":"B78","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1242\/bio.20134986","article-title":"Insights into the osteoblast precursor differentiation towards mature osteoblasts induced by continuous BMP-2 signaling","volume":"2","author":"Zouani","year":"2013","journal-title":"Biol. Open"}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2023.1141738\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T06:38:39Z","timestamp":1701067119000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2023.1141738\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,27]]},"references-count":78,"alternative-id":["10.3389\/fcell.2023.1141738"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2023.1141738","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,27]]},"article-number":"1141738"}}