{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:50:35Z","timestamp":1790142635247,"version":"4.0.1"},"reference-count":50,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32371371"],"award-info":[{"award-number":["32371371"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072106"],"award-info":[{"award-number":["82072106"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81772017"],"award-info":[{"award-number":["81772017"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32371371"],"award-info":[{"award-number":["32371371"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82072106"],"award-info":[{"award-number":["82072106"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["81772017"],"award-info":[{"award-number":["81772017"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"the Natural Science Basic Research Plan in Shaanxi Province","award":["2023-JC-YB-163"],"award-info":[{"award-number":["2023-JC-YB-163"]}]},{"name":"the Natural Science Basic Research Plan in Shaanxi Province","award":["2018JM3040"],"award-info":[{"award-number":["2018JM3040"]}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"crossref","award":["2018T111099"],"award-info":[{"award-number":["2018T111099"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"crossref","award":["2017M610653"],"award-info":[{"award-number":["2017M610653"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2018T111099"],"award-info":[{"award-number":["2018T111099"]}],"id":[{"id":"https:\/\/ror.org\/0426zh255","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2017M610653"],"award-info":[{"award-number":["2017M610653"]}],"id":[{"id":"https:\/\/ror.org\/0426zh255","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Decreased osteoblast differentiation contributes to bone loss induced by mechanical unloading. However, the underlying mechanism is still unclear. We previously found that microtubule actin crosslinking factor 1 (MACF1), a key cytoskeletal protein, plays an important role in regulating osteoblast differentiation, while the role of MACF1 in mechanical unloading suppressing osteoblast differentiation remains unclear. Here, an MACF1-knockdown (MACF1-KD) osteoblast cell line and primary osteoblasts were subjected to mechanical unloading conducted by a random positioning machine (RPM). Osteoblast differentiation was evaluated by alkaline phosphatase (ALP) staining and real-time PCR. F-actin distribution was examined by immunofluorescence staining. Western blot was adopted to detect the protein levels. Moreover, cytochalasin B and PD98059 were applied to disrupt F-actin and inhibit extracellular signal-regulated kinase (ERK) activity, respectively, to confirm the mechanism. The results show that MACF1 is significantly downregulated in osteoblasts by mechanical unloading together with decreased osteoblast differentiation. MACF1-KD osteoblasts exhibit reduced differentiation capacity and are insensitive to mechanical unloading. Mechanistically, MACF1 mediates the suppression of mechanical unloading on osteoblast differentiation by regulating F-actin distribution and the downstream ERK\/Runx2 signaling. Furthermore, F-actin disruption and ERK inhibition assays confirm that MACF1 mediates the impairment of mechanical unloading on osteoblast differentiation via the F-actin\/ERK\/Runx2 axis. In conclusion, this study reveals MACF1 as a mechanotransduction mediator for mechanical unloading, inhibiting osteoblast differentiation via F-actin\/ERK\/Runx2, and contributes to a novel mechanistic insight of cell mechanotransduction.<\/jats:p>","DOI":"10.3390\/cells15161448","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T16:30:32Z","timestamp":1786465832000},"page":"1448","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["MACF1 Mediates the Impairment of Mechanical Unloading on Osteoblast Differentiation via F-Actin\/ERK\/Runx2 Axis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1648-4428","authenticated-orcid":false,"given":"Lifang","family":"Hu","sequence":"first","affiliation":[{"name":"Lab for Bone Metabolism, Xi\u2019an Key Laboratory of Special Medicine and Health Engineering, Key Lab for Space Biosciences and Biotechnology, Research Center for Special Medicine and Health Systems Engineering, School of Life Science and Technology, Northwestern Polytechnical University, Xi\u2019an 710072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1488-6762","authenticated-orcid":false,"given":"Kang","family":"Ru","sequence":"additional","affiliation":[{"name":"Lab for Bone Metabolism, Xi\u2019an Key Laboratory of Special Medicine and Health Engineering, Key Lab for Space Biosciences and Biotechnology, Research Center for Special Medicine and Health Systems Engineering, School of Life Science and Technology, Northwestern Polytechnical University, Xi\u2019an 710072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjin","family":"Zhong","sequence":"additional","affiliation":[{"name":"Lab for Bone Metabolism, Xi\u2019an Key Laboratory of Special Medicine and Health Engineering, Key Lab for Space Biosciences and Biotechnology, Research Center for Special Medicine and Health Systems Engineering, School of Life Science and Technology, Northwestern Polytechnical University, Xi\u2019an 710072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Wang","sequence":"additional","affiliation":[{"name":"Lab for Bone Metabolism, Xi\u2019an Key Laboratory of Special Medicine and Health Engineering, Key Lab for Space Biosciences and Biotechnology, Research Center for Special Medicine and Health Systems Engineering, School of Life Science and Technology, Northwestern Polytechnical University, Xi\u2019an 710072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zizhan","family":"Huang","sequence":"additional","affiliation":[{"name":"Lab for Bone Metabolism, Xi\u2019an Key Laboratory of Special Medicine and Health Engineering, Key Lab for Space Biosciences and Biotechnology, Research Center for Special Medicine and Health Systems Engineering, School of Life Science and Technology, Northwestern Polytechnical University, Xi\u2019an 710072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2907-7629","authenticated-orcid":false,"given":"Lei","family":"Qiao","sequence":"additional","affiliation":[{"name":"Lab for Bone Metabolism, Xi\u2019an Key Laboratory of Special Medicine and Health Engineering, Key Lab for Space Biosciences and Biotechnology, Research Center for Special Medicine and Health Systems Engineering, School of Life Science and Technology, Northwestern Polytechnical University, Xi\u2019an 710072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0128-1409","authenticated-orcid":false,"given":"Zhihao","family":"Chen","sequence":"additional","affiliation":[{"name":"Lab for Bone Metabolism, Xi\u2019an Key Laboratory of Special Medicine and Health Engineering, Key Lab for Space Biosciences and Biotechnology, Research Center for Special Medicine and Health Systems Engineering, School of Life Science and Technology, Northwestern Polytechnical University, Xi\u2019an 710072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0740-9218","authenticated-orcid":false,"given":"Airong","family":"Qian","sequence":"additional","affiliation":[{"name":"Lab for Bone Metabolism, Xi\u2019an Key Laboratory of Special Medicine and Health Engineering, Key Lab for Space Biosciences and Biotechnology, Research Center for Special Medicine and Health Systems Engineering, School of Life Science and Technology, Northwestern Polytechnical University, Xi\u2019an 710072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nature01660","article-title":"Control of osteoblast function and regulation of bone mass","volume":"423","author":"Harada","year":"2003","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Liu, Z., Wang, Q., Zhang, J., Qi, S., Duan, Y., and Li, C. (2023). The Mechanotransduction Signaling Pathways in the Regulation of Osteogenesis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241814326"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/35015116","article-title":"Effects of mechanical forces on maintenance and adaptation of form in trabecular bone","volume":"405","author":"Huiskes","year":"2000","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s00223-020-00724-0","article-title":"Bone\u2019s Response to Mechanical Loading in Aging and Osteoporosis: Molecular Mechanisms","volume":"107","author":"Carina","year":"2020","journal-title":"Calcif. Tissue Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1126\/science.150643","article-title":"Inhibition of bone formation during space flight","volume":"201","author":"Morey","year":"1978","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.bone.2009.08.051","article-title":"Prevention of bone loss during 56 days of strict bed rest by side-alternating resistive vibration exercise","volume":"46","author":"Rittweger","year":"2010","journal-title":"Bone"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1177\/10454411010120030401","article-title":"The impact of microgravity on bone metabolism in vitro and in vivo","volume":"12","author":"Loomer","year":"2001","journal-title":"Crit. Rev. Oral Biol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/nrrheum.2018.37","article-title":"Skeletal changes during and after spaceflight","volume":"14","author":"Vico","year":"2018","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/nm.3026","article-title":"miR-214 targets ATF4 to inhibit bone formation","volume":"19","author":"Wang","year":"2013","journal-title":"Nat. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/s41419-017-0210-5","article-title":"Osteoblast-targeted delivery of miR-33-5p attenuates osteopenia development induced by mechanical unloading in mice","volume":"9","author":"Wang","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.bbrc.2019.11.057","article-title":"MiR-30 family members inhibit osteoblast differentiation by suppressing Runx2 under unloading conditions in MC3T3-E1 cells","volume":"522","author":"Zhang","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10096","DOI":"10.1096\/fj.202000216R","article-title":"Irisin prevents microgravity-induced impairment of osteoblast differentiation in vitro during the space flight CRS-14 mission","volume":"34","author":"Colucci","year":"2020","journal-title":"FASEB J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"0602","DOI":"10.34133\/research.0602","article-title":"Inhibition of Mitochondrial Fission Reverses Simulated Microgravity-Induced Osteoblast Dysfunction by Enhancing Mechanotransduction and Epigenetic Modification","volume":"8","author":"Shi","year":"2025","journal-title":"Research"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"110554","DOI":"10.1016\/j.cellsig.2022.110554","article-title":"Histone methyltransferase Setdb1 mediates osteogenic differentiation by suppressing the expression of miR-212-3p under mechanical unloading","volume":"102","author":"Zhang","year":"2023","journal-title":"Cell. Signal."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bai, Y., Wu, Z., Leary, S.C., Fang, C., Yu, M., Genth, H., Xie, Y., Shi, J., and Xiang, J. (2025). Focal Adhesion Kinase Alleviates Simulated Microgravity-Induced Inhibition of Osteoblast Differentiation by Activating Transcriptional Wnt\/\u03b2-Catenin-BMP2-COL1 and Metabolic SIRT1-PGC-1\u03b1-CPT1A Pathways. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26041669"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1083\/jcb.201112034","article-title":"Spectraplakins: Master orchestrators of cytoskeletal dynamics","volume":"197","author":"Suozzi","year":"2012","journal-title":"J. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"11692","DOI":"10.1038\/ncomms11692","article-title":"In vivo epidermal migration requires focal adhesion targeting of ACF7","volume":"7","author":"Yue","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1242\/jcs.196154","article-title":"Spectraplakin family proteins\u2013cytoskeletal crosslinkers with versatile roles","volume":"130","author":"Zhang","year":"2017","journal-title":"J. Cell Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7726","DOI":"10.1038\/s41598-019-44183-6","article-title":"The cytoskeletal crosslinking protein MACF1 is dispensable for thrombus formation and hemostasis","volume":"9","author":"Schurr","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1083\/jcb.201810023","article-title":"MACF1 links Rapsyn to microtubule- and actin-binding proteins to maintain neuromuscular synapses","volume":"218","author":"Oury","year":"2019","journal-title":"J. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.cell.2010.12.033","article-title":"Skin stem cells orchestrate directional migration by regulating microtubule-ACF7 connections through GSK3\u03b2","volume":"144","author":"Wu","year":"2011","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Cusseddu, R., Robert, A., and Cote, J.F. (2021). Strength Through Unity: The Power of the Mega-Scaffold MACF1. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.641727"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"583","DOI":"10.5483\/BMBRep.2015.48.10.098","article-title":"Knockdown of microtubule actin crosslinking factor 1 inhibits cell proliferation in MC3T3-E1 osteoblastic cells","volume":"48","author":"Hu","year":"2015","journal-title":"BMB Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1002\/jcp.26059","article-title":"Microtubule actin crosslinking factor 1 promotes osteoblast differentiation by promoting \u03b2-catenin\/TCF1\/Runx2 signaling axis","volume":"233","author":"Hu","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2160","DOI":"10.1038\/s41418-021-00744-9","article-title":"MACF1 promotes osteoblast differentiation by sequestering repressors in cytoplasm","volume":"28","author":"Hu","year":"2021","journal-title":"Cell Death Differ."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1089\/hum.2017.153","article-title":"MACF1 Overexpression by Transfecting the 21 kbp Large Plasmid PEGFP-C1A-ACF7 Promotes Osteoblast Differentiation and Bone Formation","volume":"29","author":"Zhang","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1111\/jcmm.14729","article-title":"Deficiency of Macf1 in osterix expressing cells decreases bone formation by Bmp2\/Smad\/Runx2 pathway","volume":"24","author":"Qiu","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"12263","DOI":"10.7150\/thno.53009","article-title":"Silencing of miR-138-5p sensitizes bone anabolic action to mechanical stimuli","volume":"10","author":"Chen","year":"2020","journal-title":"Theranostics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.asr.2012.07.036","article-title":"Inhibitory effect of simulated microgravity on differentiating preosteoblasts","volume":"51","author":"Hu","year":"2013","journal-title":"Adv. Space Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Hendesi, H., Barbe, M.F., Safadi, F.F., Monroy, M.A., and Popoff, S.N. (2015). Integrin Mediated Adhesion of Osteoblasts to Connective Tissue Growth Factor (CTGF\/CCN2) Induces Cytoskeleton Reorganization and Cell Differentiation. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0115325"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/978-1-4939-6424-6_16","article-title":"Quantifying Tensile Force and ERK Phosphorylation on Actin Stress Fibers","volume":"Volume 1487","author":"Hirata","year":"2017","journal-title":"Methods Molecular Biology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1083\/jcb.200610046","article-title":"Critical role of the extracellular signal-regulated kinase-MAPK pathway in osteoblast differentiation and skeletal development","volume":"176","author":"Ge","year":"2007","journal-title":"J. Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/j.ajhg.2018.10.019","article-title":"MACF1 Mutations Encoding Highly Conserved Zinc-Binding Residues of the GAR Domain Cause Defects in Neuronal Migration and Axon Guidance","volume":"103","author":"Dobyns","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1007\/s11010-022-04517-x","article-title":"The role of MACF1 on acute myeloid leukemia cell proliferation is involved in Runx2-targeted PI3K\/Akt signaling","volume":"478","author":"Wang","year":"2023","journal-title":"Mol. Cell. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Fassett, J.T., Xu, X., Kwak, D., Wang, H., Liu, X., Hu, X., Bache, R.J., and Chen, Y. (2013). Microtubule Actin Cross-linking Factor 1 regulates cardiomyocyte microtubule distribution and adaptation to hemodynamic overload. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073887"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1083\/jcb.147.6.1275","article-title":"Microtubule actin cross-linking factor (MACF): A hybrid of dystonin and dystrophin that can interact with the actin and microtubule cytoskeletons","volume":"147","author":"Leung","year":"1999","journal-title":"J. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1096\/fasebj.13.9001.s3","article-title":"How cells (might) sense microgravity","volume":"13","author":"Ingber","year":"1999","journal-title":"FASEB J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.bbrc.2006.07.073","article-title":"Reorganization of actin filaments enhances chondrogenic differentiation of cells derived from murine embryonic stem cells","volume":"348","author":"Zhang","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1006\/bbrc.2000.2987","article-title":"Disruption of actin cytoskeleton induces chondrogenesis of mesenchymal cells by activating protein kinase C-alpha signaling","volume":"273","author":"Lim","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1007\/s00774-009-0037-y","article-title":"Transient dynamic actin cytoskeletal change stimulates the osteoblastic differentiation","volume":"27","author":"Higuchi","year":"2009","journal-title":"J. Bone Miner. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"105630","DOI":"10.1016\/j.jmbbm.2022.105630","article-title":"Changes in the intra- and extra-mechanical environment of the nucleus in Saos-2 osteoblastic cells during bone differentiation process: Nuclear shrinkage and stiffening in cell differentiation","volume":"138","author":"Nagayama","year":"2023","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"32533","DOI":"10.1074\/jbc.M109.040980","article-title":"Identification and functional characterization of ERK\/MAPK phosphorylation sites in the Runx2 transcription factor","volume":"284","author":"Ge","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1002\/jcb.20958","article-title":"Regulation of osteoblast differentiation by transcription factors","volume":"99","author":"Komori","year":"2006","journal-title":"J. Cell. Biochem."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Komori, T. (2024). Regulation of Skeletal Development and Maintenance by Runx2 and Sp7. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms251810102"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/bs.apcsb.2016.11.002","article-title":"Chapter Four\u2013NF-\u03baB as a Therapeutic Target in Inflammatory-Associated Bone Diseases","volume":"Volume 107","author":"Donev","year":"2017","journal-title":"Advances in Protein Chemistry and Structural Biology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"124365","DOI":"10.1016\/j.lfs.2026.124365","article-title":"The posttranslational modification landscape of transcription factors in osteoblast differentiation and bone formation","volume":"394","author":"Kang","year":"2026","journal-title":"Life Sci."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Kugimiya, F., Kawaguchi, H., Ohba, S., Kawamura, N., Hirata, M., Chikuda, H., Azuma, Y., Woodgett, J.R., Nakamura, K., and Chung, U.I. (2007). GSK-3\u03b2 controls osteogenesis through regulating Runx2 activity. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0000837"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.molcel.2005.06.009","article-title":"Erk associates with and primes GSK-3\u03b2 for its inactivation resulting in upregulation of \u03b2-catenin","volume":"19","author":"Ding","year":"2005","journal-title":"Mol. Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1007\/s13238-012-2058-x","article-title":"Suppression of GSK3\u03b2 by ERK mediates lipopolysaccharide induced cell migration in macrophage through \u03b2-catenin signaling","volume":"3","author":"Gong","year":"2012","journal-title":"Protein Cell"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/16\/1448\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T04:20:57Z","timestamp":1786594857000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/16\/1448"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,11]]},"references-count":50,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["cells15161448"],"URL":"https:\/\/doi.org\/10.3390\/cells15161448","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,11]]}}}