{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:22:08Z","timestamp":1790785328658,"version":"4.1.0"},"reference-count":78,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T00:00:00Z","timestamp":1700611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Protestant Hospital of Bethel Foundation, University Hospital OWL of Bielefeld University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Sex-related differences are a current topic in contemporary science. In addition to hormonal regulation, cell-autonomous mechanisms are important in bone homeostasis and regeneration. In this study, human skeletal stem cells (SSCs) from female and male adults were cultured and analyzed with immunological assays and osteogenic differentiation assessments. Female SSCs exhibited a mean doubling time of 100.6 h, whereas male SSCs displayed a mean doubling time of 168.0 h. Immunophenotyping revealed the expression of the stem cell markers Nestin, CD133, and CD164, accompanied by the neural-crest marker SOX9. Furthermore, multiparameter flow cytometric analyses revealed a substantial population of multipotent SSCs, comprising up to 80% in both sexes. An analysis of the osteogenic differentiation potential demonstrated a strong mineralization in both male and female SSCs under physiological conditions. Recognizing the prevailing association of bone diseases with inflammatory processes, we also analyzed the osteogenic potential of SSCs from both sexes under pro-inflammatory conditions. Upon TNF-\u03b1 and IL-1\u03b2 treatment, we observed no sexual dimorphism on osteogenesis. In summary, we demonstrated the successful isolation and characterization of SSCs capable of rapid osteogenic differentiation. Taken together, in vitro cultured SSCs might be a suitable model to study sexual dimorphisms and develop drugs for degenerative bone diseases.<\/jats:p>","DOI":"10.3390\/cells12232683","type":"journal-article","created":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T08:47:43Z","timestamp":1700642863000},"page":"2683","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Analyzing Sex-Specific Dimorphism in Human Skeletal Stem Cells"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0383-4249","authenticated-orcid":false,"given":"Tarek","family":"Niemann","sequence":"first","affiliation":[{"name":"Molecular Neurobiology, Bielefeld University, Universit\u00e4tsstrasse 25, 33615 Bielefeld, Germany"},{"name":"Forschungsverbund BioMedizin Bielefeld FBMB e.V., 33615 Bielefeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Joneleit","sequence":"additional","affiliation":[{"name":"Molecular Neurobiology, Bielefeld University, Universit\u00e4tsstrasse 25, 33615 Bielefeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Storm","sequence":"additional","affiliation":[{"name":"Forschungsverbund BioMedizin Bielefeld FBMB e.V., 33615 Bielefeld, Germany"},{"name":"Department of Cell Biology, Bielefeld University, Universit\u00e4tsstrasse 25, 33615 Bielefeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Nacke","sequence":"additional","affiliation":[{"name":"Molecular Neurobiology, Bielefeld University, Universit\u00e4tsstrasse 25, 33615 Bielefeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2352-7951","authenticated-orcid":false,"given":"Dirk","family":"W\u00e4hnert","sequence":"additional","affiliation":[{"name":"Forschungsverbund BioMedizin Bielefeld FBMB e.V., 33615 Bielefeld, Germany"},{"name":"Department of Trauma and Orthopedic Surgery, Protestant Hospital of Bethel Foundation, Campus Bielefeld-Bethel, University Hospital OWL of Bielefeld University, Burgsteig 13, 33617 Bielefeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Kaltschmidt","sequence":"additional","affiliation":[{"name":"Forschungsverbund BioMedizin Bielefeld FBMB e.V., 33615 Bielefeld, Germany"},{"name":"Department of Cell Biology, Bielefeld University, Universit\u00e4tsstrasse 25, 33615 Bielefeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Vordemvenne","sequence":"additional","affiliation":[{"name":"Forschungsverbund BioMedizin Bielefeld FBMB e.V., 33615 Bielefeld, Germany"},{"name":"Department of Trauma and Orthopedic Surgery, Protestant Hospital of Bethel Foundation, Campus Bielefeld-Bethel, University Hospital OWL of Bielefeld University, Burgsteig 13, 33617 Bielefeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Kaltschmidt","sequence":"additional","affiliation":[{"name":"Molecular Neurobiology, Bielefeld University, Universit\u00e4tsstrasse 25, 33615 Bielefeld, Germany"},{"name":"Forschungsverbund BioMedizin Bielefeld FBMB e.V., 33615 Bielefeld, Germany"},{"name":"Department of Cell Biology, Bielefeld University, Universit\u00e4tsstrasse 25, 33615 Bielefeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kim, J.-M., Lin, C., Stavre, Z., Greenblatt, M.B., and Shim, J.-H. (2020). Osteoblast-Osteoclast Communication and Bone Homeostasis. Cells, 9.","DOI":"10.3390\/cells9092073"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Noirrit-Esclassan, E., Valera, M.-C., Tremollieres, F., Arnal, J.-F., Lenfant, F., Fontaine, C., and Vinel, A. (2021). Critical Role of Estrogens on Bone Homeostasis in Both Male and Female: From Physiology to Medical Implications. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041568"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1242\/dev.102210","article-title":"Skeletal Stem Cells","volume":"142","author":"Bianco","year":"2015","journal-title":"Development"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ambrosi, T.H., Longaker, M.T., and Chan, C.K.F. (2019). A Revised Perspective of Skeletal Stem Cell Biology. Front. Cell Dev. Biol., 7.","DOI":"10.3389\/fcell.2019.00189"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s11914-020-00572-9","article-title":"Skeletal Stem Cells for Bone Development and Repair: Diversity Matters","volume":"18","author":"Matsushita","year":"2020","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Matsushita, Y., Ono, W., and Ono, N. (2021). Bone Regeneration via Skeletal Cell Lineage Plasticity: All Hands Mobilized for Emergencies: Quiescent Mature Skeletal Cells Can Be Activated in Response to Injury and Robustly Participate in Bone Regeneration through Cellular Plasticity. Bioessays, 43.","DOI":"10.1002\/bies.202000202"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.cell.2014.12.002","article-title":"Identification and Specification of the Mouse Skeletal Stem Cell","volume":"160","author":"Chan","year":"2015","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.cell.2018.07.029","article-title":"Identification of the Human Skeletal Stem Cell","volume":"175","author":"Chan","year":"2018","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.1038\/s41596-023-00836-5","article-title":"Purification and Functional Characterization of Novel Human Skeletal Stem Cell Lineages","volume":"18","author":"Hoover","year":"2023","journal-title":"Nat. Protoc."},{"key":"ref_10","first-page":"141","article-title":"A review of gender differences in proximal humerus fractures","volume":"2","author":"Pesce","year":"2016","journal-title":"J. Sex Gend. Specif. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"750","DOI":"10.5534\/wjmh.200099","article-title":"Gender Differences in Osteoporosis: A Single-Center Observational Study","volume":"39","author":"Sirufo","year":"2021","journal-title":"World J. Men\u2019s Health"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1007\/s00198-003-1422-3","article-title":"Gender Differences in Volumetric Bone Density: A Study of Opposite-Sex Twins","volume":"14","author":"Naganathan","year":"2003","journal-title":"Osteoporos. Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1186\/s13018-021-02772-0","article-title":"The Global Prevalence of Osteoporosis in the World: A Comprehensive Systematic Review and Meta-Analysis","volume":"16","author":"Salari","year":"2021","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"743","DOI":"10.2106\/JBJS.I.00919","article-title":"The Assessment of Fracture Risk","volume":"92","author":"Unnanuntana","year":"2010","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1089\/jwh.2022.0361","article-title":"Recommendations for Improving Women\u2019s Bone Health throughout the Lifespan","volume":"31","author":"McPhee","year":"2022","journal-title":"J. Womens Health"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"13361","DOI":"10.1073\/pnas.95.23.13361","article-title":"Bone Homeostasis","volume":"95","author":"Rodan","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1016\/j.stemcr.2022.06.001","article-title":"The Role of CDK8 in Mesenchymal Stem Cells in Controlling Osteoclastogenesis and Bone Homeostasis","volume":"17","author":"Yamada","year":"2022","journal-title":"Stem Cell Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1016\/j.bbamcr.2019.06.014","article-title":"Estrogen Enhances Human Osteoblast Survival and Function via Promotion of Autophagy","volume":"1866","author":"Gavali","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.tem.2012.03.008","article-title":"Estrogen and the Skeleton","volume":"23","author":"Khosla","year":"2012","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_20","first-page":"9","article-title":"Primary Osteoporosis in Postmenopausal Women","volume":"1","author":"Ji","year":"2015","journal-title":"Chronic Dis. Transl. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6491","DOI":"10.1038\/s41467-022-34063-5","article-title":"Sexually Dimorphic Estrogen Sensing in Skeletal Stem Cells Controls Skeletal Regeneration","volume":"13","author":"Andrew","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.surg.2007.04.013","article-title":"In the Adult Mesenchymal Stem Cell Population, Source Gender Is a Biologically Relevant Aspect of Protective Power","volume":"142","author":"Crisostomo","year":"2007","journal-title":"Surgery"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.bone.2015.03.001","article-title":"Osteoblast Differentiation Profiles Define Sex Specific Gene Expression Patterns in Craniosynostosis","volume":"76","author":"Park","year":"2015","journal-title":"Bone"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3338","DOI":"10.1002\/1873-3468.13606","article-title":"Sexual Dimorphisms in Adult Human Neural, Mesoderm-Derived, and Neural Crest-Derived Stem Cells","volume":"593","author":"Greiner","year":"2019","journal-title":"FEBS Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/S0306-9877(03)00326-8","article-title":"Maldaptation of the Link between Inflammation and Bone Turnover May Be a Key Determinant of Osteoporosis","volume":"63","author":"Yun","year":"2004","journal-title":"Med. Hypotheses"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1002\/jbmr.5650110802","article-title":"Estrogen, Cytokines, and Pathogenesis of Postmenopausal Osteoporosis","volume":"11","author":"Pacifici","year":"1996","journal-title":"J. Bone Miner. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S1297-319X(03)00131-3","article-title":"Role for Osteoprotegerin in Rheumatoid Inflammation","volume":"71","author":"Bessis","year":"2004","journal-title":"Jt. Bone Spine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"84","DOI":"10.18053\/jctres.02.201603.005","article-title":"The Role of TNF-\u03b1 in Rheumatoid Arthritis: A Focus on Regulatory T Cells","volume":"2","author":"Farrugia","year":"2016","journal-title":"J. Clin. Transl. Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kaltschmidt, C., Greiner, J.F.W., and Kaltschmidt, B. (2021). The Transcription Factor NF-\u03baB in Stem Cells and Development. Cells, 10.","DOI":"10.3390\/cells10082042"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1136\/ard.16.4.494","article-title":"Radiological Assessment of Osteo-Arthrosis","volume":"16","author":"Kellgren","year":"1957","journal-title":"Ann. Rheum. Dis."},{"key":"ref_31","first-page":"75","article-title":"A Method of Estimation of the Cell Doubling Time on Basis of the Cell Culture Monitoring Data","volume":"28","author":"Zychowicz","year":"2008","journal-title":"Biocybern. Biomed. Eng."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.nano.2019.01.018","article-title":"Natural and Synthetic Nanopores Directing Osteogenic Differentiation of Human Stem Cells","volume":"17","author":"Greiner","year":"2019","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ab.2004.02.002","article-title":"An Alizarin Red-Based Assay of Mineralization by Adherent Cells in Culture: Comparison with Cetylpyridinium Chloride Extraction","volume":"329","author":"Gregory","year":"2004","journal-title":"Anal. Biochem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1007\/s12015-012-9417-0","article-title":"Phenol Red Inhibits Chondrogenic Differentiation and Affects Osteogenic Differentiation of Human Mesenchymal Stem Cells in Vitro","volume":"9","author":"Lysdahl","year":"2013","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Siegel, G., Kluba, T., Hermanutz-Klein, U., Bieback, K., Northoff, H., and Sch\u00e4fer, R. (2013). Phenotype, Donor Age and Gender Affect Function of Human Bone Marrow-Derived Mesenchymal Stromal Cells. BMC Med., 11.","DOI":"10.1186\/1741-7015-11-146"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1007\/s00774-010-0215-y","article-title":"Human Mesenchymal Stem Cell Proliferation and Osteogenic Differentiation during Long-Term Ex Vivo Cultivation Is Not Age Dependent","volume":"29","author":"Fickert","year":"2011","journal-title":"J. Bone Miner. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1007\/s00277-012-1438-x","article-title":"Donor Age and Long-Term Culture Affect Differentiation and Proliferation of Human Bone Marrow Mesenchymal Stem Cells","volume":"91","author":"Zaim","year":"2012","journal-title":"Ann. Hematol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1089\/scd.2008.0338","article-title":"CD133 as a Marker for Cancer Stem Cells: Progresses and Concerns","volume":"18","author":"Wu","year":"2009","journal-title":"Stem Cells Dev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"762098","DOI":"10.1155\/2015\/762098","article-title":"Characterization of Nestin, a Selective Marker for Bone Marrow Derived Mesenchymal Stem Cells","volume":"2015","author":"Xie","year":"2015","journal-title":"Stem Cells Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1002\/jcb.21423","article-title":"Skeletal Stem\/Osteoprogenitor Cells: Current Concepts, Alternate Hypotheses, and Relationship to the Bone Remodeling Compartment","volume":"103","author":"Khosla","year":"2008","journal-title":"J. Cell. Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1089\/scd.2006.15.286","article-title":"Neural Crest As the Source of Adult Stem Cells","volume":"15","author":"Pierret","year":"2006","journal-title":"Stem Cells Dev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"266","DOI":"10.5966\/sctm.2011-0042","article-title":"Human Neural Crest Stem Cells Derived from Human ESCs and Induced Pluripotent Stem Cells: Induction, Maintenance, and Differentiation into Functional Schwann Cells","volume":"1","author":"Liu","year":"2012","journal-title":"Stem Cells Transl. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1089\/scd.2011.0419","article-title":"Isolation of Novel Multipotent Neural Crest-Derived Stem Cells from Adult Human Inferior Turbinate","volume":"21","author":"Hauser","year":"2012","journal-title":"Stem Cells Dev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.devcel.2011.12.024","article-title":"Sox9 Directs Hypertrophic Maturation and Blocks Osteoblast Differentiation of Growth Plate Chondrocytes","volume":"22","author":"Dy","year":"2012","journal-title":"Dev. Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"13551","DOI":"10.1038\/s41598-018-31853-0","article-title":"Runx2 Is Required for the Proliferation of Osteoblast Progenitors and Induces Proliferation by Regulating Fgfr2 and Fgfr3","volume":"8","author":"Kawane","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.ctdb.2019.01.006","article-title":"Stem and Progenitor Cells in Skeletal Development","volume":"133","author":"Ono","year":"2019","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.cell.2007.08.025","article-title":"Self-Renewing Osteoprogenitors in Bone Marrow Sinusoids Can Organize a Hematopoietic Microenvironment","volume":"131","author":"Sacchetti","year":"2007","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2774","DOI":"10.1002\/jbm.a.36780","article-title":"Specific Concentration of Hyaluronan Amide Derivative Induces Osteogenic Mineralization of Human Mesenchymal Stromal Cells: Evidence of RUNX2 and COL1A1 Genes Modulation","volume":"107","author":"Paolella","year":"2019","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"12724","DOI":"10.1021\/acsomega.1c07225","article-title":"Alkaline Phosphatase Activity of Serum Affects Osteogenic Differentiation Cultures","volume":"7","author":"Ansari","year":"2022","journal-title":"ACS Omega"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/stem.1567","article-title":"An Osteopontin-Integrin Interaction Plays a Critical Role in Directing Adipogenesis and Osteogenesis by Mesenchymal Stem Cells","volume":"32","author":"Chen","year":"2014","journal-title":"Stem Cells"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2202163","DOI":"10.1002\/adhm.202202163","article-title":"Transcriptomic Changes toward Osteogenic Differentiation of Mesenchymal Stem Cells on 3D-Printed GelMA\/CNC Hydrogel under Pulsatile Pressure Environment","volume":"12","author":"Ganguly","year":"2023","journal-title":"Adv. Healthc. Mater."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1007\/s12178-022-09803-1","article-title":"Sex-Based Difference in Bone Healing: A Review of Recent Pre-Clinical Literature","volume":"15","author":"Kurapaty","year":"2022","journal-title":"Curr. Rev. Musculoskelet. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.jpeds.2016.09.056","article-title":"The Determinants of Peak Bone Mass","volume":"180","author":"Gordon","year":"2017","journal-title":"J. Pediatr."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1385\/JCD:3:2:177","article-title":"Bone Mineral Density in Diagnosis of Osteoporosis: Reference Population, Definition of Peak Bone Mass, and Measured Site Determine Prevalence","volume":"3","author":"Larsson","year":"2000","journal-title":"J. Clin. Densitom."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1002\/jbmr.4270","article-title":"Sexual Dimorphism in Differentiating Osteoclast Precursors Demonstrates Enhanced Inflammatory Pathway Activation in Female Cells","volume":"36","author":"Mun","year":"2021","journal-title":"J. Bone Miner. Res."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Lorenzo, J. (2020). Sexual Dimorphism in Osteoclasts. Cells, 9.","DOI":"10.3390\/cells9092086"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"499e","DOI":"10.1097\/PRS.0000000000000056","article-title":"Estrogen as a Novel Agent for Induction of Adipose-Derived Mesenchymal Stem Cells for Osteogenic Differentiation: In Vivo Bone Tissue-Engineering Study","volume":"133","author":"Calis","year":"2014","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/scrt515","article-title":"17beta-Estradiol Promotes the Odonto\/Osteogenic Differentiation of Stem Cells from Apical Papilla via Mitogen-Activated Protein Kinase Pathway","volume":"5","author":"Li","year":"2014","journal-title":"Stem Cell Res. Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1089\/ten.2006.12.2747","article-title":"Modulations of 17-Beta Estradiol on Osteogenic and Adipogenic Differentiations of Human Mesenchymal Stem Cells","volume":"12","author":"Hong","year":"2006","journal-title":"Tissue Eng."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.jsbmb.2009.02.001","article-title":"Steroid Regulation of Proliferation and Osteogenic Differentiation of Bone Marrow Stromal Cells: A Gender Difference","volume":"114","author":"Hong","year":"2009","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2496","DOI":"10.1073\/pnas.83.8.2496","article-title":"Phenol Red in Tissue Culture Media Is a Weak Estrogen: Implications Concerning the Study of Estrogen-Responsive Cells in Culture","volume":"83","author":"Berthois","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Lee, H.-J., Lee, H., Na, C.-B., Song, I.-S., Ryu, J.-J., and Park, J.-B. (2021). Evaluation of the Age- and Sex-Related Changes of the Osteogenic Differentiation Potentials of Healthy Bone Marrow-Derived Mesenchymal Stem Cells. Medicina, 57.","DOI":"10.3390\/medicina57060520"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/S1001-9294(15)30021-3","article-title":"Dynamic Expression Profiles of Marker Genes in Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells","volume":"30","author":"Wang","year":"2015","journal-title":"Chin. Med. Sci. J."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Karadjian, M., Senger, A.-S., Essers, C., Wilkesmann, S., Heller, R., Fellenberg, J., Simon, R., and Westhauser, F. (2020). Human Platelet Lysate Can Replace Fetal Calf Serum as a Protein Source to Promote Expansion and Osteogenic Differentiation of Human Bone-Marrow-Derived Mesenchymal Stromal Cells. Cells, 9.","DOI":"10.3390\/cells9040918"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"9919361","DOI":"10.1155\/2021\/9919361","article-title":"An In Vitro and In Vivo Comparison of Osteogenic Differentiation of Human Mesenchymal Stromal\/Stem Cells","volume":"2021","author":"Mollentze","year":"2021","journal-title":"Stem Cells Int."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41586-018-0554-8","article-title":"Discovery of a Periosteal Stem Cell Mediating Intramembranous Bone Formation","volume":"562","author":"Debnath","year":"2018","journal-title":"Nature"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-\u03baB Signaling in Inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Su, J., Zhao, P., Kong, L., Li, X., Yan, J., Zeng, Y., and Li, Y. (2013). Trichothecin Induces Cell Death in NF-\u03baB Constitutively Activated Human Cancer Cells via Inhibition of IKK\u03b2 Phosphorylation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0071333"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e61965","DOI":"10.7554\/eLife.61965","article-title":"Sustained TNF-\u03b1 Stimulation Leads to Transcriptional Memory That Greatly Enhances Signal Sensitivity and Robustness","volume":"9","author":"Zhao","year":"2020","journal-title":"eLife"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"32606","DOI":"10.1074\/jbc.272.51.32606","article-title":"Activation of Nuclear Transcription Factor NF-\u03baB by Interleukin-1 Is Accompanied by Casein Kinase II-Mediated Phosphorylation of the P65 Subunit","volume":"272","author":"Bird","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.3389\/fimmu.2018.01931","article-title":"Sex Hormones Determine Immune Response","volume":"9","author":"Taneja","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1111\/acel.12326","article-title":"How Sex and Age Affect Immune Responses, Susceptibility to Infections, and Response to Vaccination","volume":"14","author":"Berger","year":"2015","journal-title":"Aging Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1152\/advan.00065.2006","article-title":"A Role for Transcription Factor NF-\u03baB in Autoimmunity: Possible Interactions of Genes, Sex, and the Immune Response","volume":"30","author":"Dale","year":"2006","journal-title":"Adv. Physiol. Educ."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1007\/s13577-022-00711-7","article-title":"Regulation of Osteogenic Differentiation by the Pro-Inflammatory Cytokines IL-1\u03b2 and TNF-\u03b1: Current Conclusions and Controversies","volume":"35","author":"Mo","year":"2022","journal-title":"Hum. Cell"},{"key":"ref_75","first-page":"601","article-title":"Osteoporosis: Differences and Similarities in Male and Female Patients","volume":"37","author":"Lane","year":"2006","journal-title":"Orthop. Clin."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.5435\/00124635-200700001-00007","article-title":"Sex Differences in Osteoarthritis of the Hip and Knee","volume":"15","year":"2007","journal-title":"JAAOS J. Am. Acad. Orthop. Surg."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41413-020-0102-7","article-title":"Aging and Menopause Reprogram Osteoclast Precursors for Aggressive Bone Resorption","volume":"8","author":"Olesen","year":"2020","journal-title":"Bone Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/j.bbrc.2003.10.095","article-title":"Osteoblast Recruitment from Stem Cells Does Not Decrease by Age at Late Adulthood","volume":"311","author":"Risteli","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/23\/2683\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:27:19Z","timestamp":1760131639000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/23\/2683"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,22]]},"references-count":78,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["cells12232683"],"URL":"https:\/\/doi.org\/10.3390\/cells12232683","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,22]]}}}