{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T03:28:07Z","timestamp":1792466887534,"version":"4.5.0"},"reference-count":152,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,1,23]],"date-time":"2019-01-23T00:00:00Z","timestamp":1548201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Articular cartilage covers the surface of synovial joints and enables joint movement. However, it is susceptible to progressive degeneration with age that can be accelerated by either previous joint injury or meniscectomy. This degenerative disease is known as osteoarthritis (OA) and it greatly affects the adult population. Cell-based tissue engineering provides a possible solution for treating OA at its earliest stages, particularly focal cartilage lesions. A candidate cell type for treating these focal defects are Mesenchymal Stem Cells (MSCs). However, present methods for differentiating these cells towards the chondrogenic lineage lead to hypertrophic chondrocytes and bone formation in vivo. Environmental stimuli that can stabilise the articular chondrocyte phenotype without compromising tissue formation have been extensively investigated. One factor that has generated intensive investigation in MSC chondrogenesis is low oxygen tension or physioxia (2\u20135% oxygen). In vivo articular cartilage resides at oxygen tensions between 1\u20134%, and in vitro results suggest that these conditions are beneficial for MSC expansion and chondrogenesis, particularly in suppressing the cartilage hypertrophy. This review will summarise the current literature regarding the effects of physioxia on MSC chondrogenesis with an emphasis on the pathways that control tissue formation and cartilage hypertrophy.<\/jats:p>","DOI":"10.3390\/ijms20030484","type":"journal-article","created":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T03:52:32Z","timestamp":1548301952000},"page":"484","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":77,"title":["The Importance of Physioxia in Mesenchymal Stem Cell Chondrogenesis and the Mechanisms Controlling Its Response"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7647-3769","authenticated-orcid":false,"given":"Girish","family":"Pattappa","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Trauma Surgery, Department of Trauma Surgery, University Hospital Regensburg, Franz Josef Strauss Allee 11, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Johnstone","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Rehabilitation, Oregon Health &amp; Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Zellner","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Trauma Surgery, Department of Trauma Surgery, University Hospital Regensburg, Franz Josef Strauss Allee 11, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7588-1290","authenticated-orcid":false,"given":"Denitsa","family":"Docheva","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Trauma Surgery, Department of Trauma Surgery, University Hospital Regensburg, Franz Josef Strauss Allee 11, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Angele","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Trauma Surgery, Department of Trauma Surgery, University Hospital Regensburg, Franz Josef Strauss Allee 11, 93053 Regensburg, Germany"},{"name":"Sporthopaedicum Regensburg, Hildegard von Bingen Strasse 1, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1177\/1941738109350438","article-title":"The basic science of articular cartilage: Structure, composition, and function","volume":"1","author":"Bedi","year":"2009","journal-title":"Sports Health"},{"key":"ref_2","first-page":"465","article-title":"Articular cartilage and osteoarthritis","volume":"54","author":"Buckwalter","year":"2005","journal-title":"Instr. Course Lect."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/s11926-000-0021-y","article-title":"Osteoarthritis and cartilage: The role of cytokines","volume":"2","author":"Goldring","year":"2000","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"202","DOI":"10.22203\/eCM.v021a16","article-title":"Roles of inflammatory and anabolic cytokines in cartilage metabolism: Signals and multiple effectors converge upon MMP-13 regulation in osteoarthritis","volume":"21","author":"Goldring","year":"2011","journal-title":"Eur. Cell Mater."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1016\/S0020-1383(15)30012-7","article-title":"Defect type, localization and marker gene expression determines early adverse events of matrix-associated autologous chondrocyte implantation","volume":"46","author":"Angele","year":"2015","journal-title":"Injury"},{"key":"ref_6","first-page":"67","article-title":"The German Cartilage Registry (KnorpelRegister DGOU) for evaluation of surgical treatment for cartilage defects: Experience after six months including first demographic data","volume":"153","author":"Niemeyer","year":"2015","journal-title":"Z. Orthop. Unfall."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1007\/s00167-016-4068-3","article-title":"Early osteoarthritis of the knee","volume":"24","author":"Madry","year":"2016","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/s00167-011-1743-2","article-title":"Definition and classification of early osteoarthritis of the knee","volume":"20","author":"Luyten","year":"2012","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s00167-011-1705-8","article-title":"Biological aspects of early osteoarthritis","volume":"20","author":"Madry","year":"2012","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1002\/jor.22334","article-title":"Synovial fluid concentrations and relative potency of interleukin-1 alpha and beta in cartilage and meniscus degradation","volume":"31","author":"McNulty","year":"2013","journal-title":"J. Orthop. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1056\/NEJM199410063311401","article-title":"Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation","volume":"331","author":"Brittberg","year":"1994","journal-title":"N. Engl. J. Med."},{"key":"ref_12","first-page":"38","article-title":"Autologous chondrocyte implantation (ACI) for cartilage defects of the knee: A guideline by the working group \u201cTissue Regeneration\u201d of the German Society of Orthopaedic Surgery and Traumatology (DGOU)","volume":"151","author":"Niemeyer","year":"2013","journal-title":"Z. Orthop. Unfall."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1126\/science.284.5411.143","article-title":"Multilineage potential of adult human mesenchymal stem cells","volume":"284","author":"Pittenger","year":"1999","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1002\/jor.1100090504","article-title":"Mesenchymal stem cells","volume":"9","author":"Caplan","year":"1991","journal-title":"J. Orthop. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1080\/14653240310003026","article-title":"Adipose-derived adult stem cells: Isolation, characterization, and differentiation potential","volume":"5","author":"Gimble","year":"2003","journal-title":"Cytotherapy"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1002\/art.21212","article-title":"Comparison of human stem cells derived from various mesenchymal tissues: Superiority of synovium as a cell source","volume":"52","author":"Sakaguchi","year":"2005","journal-title":"Arthritis Rheumatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1006\/excr.1997.3858","article-title":"In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells","volume":"238","author":"Johnstone","year":"1998","journal-title":"Exp. Cell Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.2106\/00004623-199812000-00004","article-title":"The chondrogenic potential of human bone-marrow-derived mesenchymal progenitor cells","volume":"80","author":"Yoo","year":"1998","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3254","DOI":"10.1002\/art.22136","article-title":"Premature induction of hypertrophy during in vitro chondrogenesis of human mesenchymal stem cells correlates with calcification and vascular invasion after ectopic transplantation in SCID mice","volume":"54","author":"Pelttari","year":"2006","journal-title":"Arthritis Rheumatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/j.1365-2613.2010.00707.x","article-title":"Lack of oxygen in articular cartilage: Consequences for chondrocyte biology","volume":"91","author":"Lafont","year":"2010","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"719","DOI":"10.2106\/00004623-197153040-00011","article-title":"Oxygen tension in zones of the epiphyseal plate, the metaphysis and diaphysis. An in vitro and in vivo study in rats and rabbits","volume":"53","author":"Brighton","year":"1971","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1002\/art.1780130606","article-title":"Oxygen tension in synovial fluids","volume":"13","year":"1970","journal-title":"Arthritis Rheumatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"801","DOI":"10.7326\/0003-4819-58-5-801","article-title":"Bone marrow gas tensions, bone marrow blood flow, and erythropoiesis in man","volume":"58","author":"Grant","year":"1963","journal-title":"Ann. Intern. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3915","DOI":"10.1002\/art.20675","article-title":"Factors influencing the oxygen concentration gradient from the synovial surface of articular cartilage to the cartilage-bone interface: A modeling study","volume":"50","author":"Zhou","year":"2004","journal-title":"Arthritis Rheumatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4778","DOI":"10.1074\/jbc.M707729200","article-title":"Hypoxia promotes the differentiated human articular chondrocyte phenotype through SOX9-dependent and -independent pathways","volume":"283","author":"Lafont","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3297","DOI":"10.1002\/art.22878","article-title":"Hypoxia-inducible factor 2\u03b1 is essential for hypoxic induction of the human articular chondrocyte phenotype","volume":"56","author":"Lafont","year":"2007","journal-title":"Arthritis Rheumatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3109\/03008200109014251","article-title":"Effect of oxygen tension on chondrocyte extracellular matrix accumulation","volume":"42","author":"Murphy","year":"2001","journal-title":"Connect. Tissue Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1089\/107632701753337735","article-title":"Effect of oxygen tension and alginate encapsulation on restoration of the differentiated phenotype of passaged chondrocytes","volume":"7","author":"Murphy","year":"2001","journal-title":"Tissue Eng."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1002\/art.37867","article-title":"Hypoxia promotes the production and inhibits the destruction of human articular cartilage","volume":"65","author":"Thoms","year":"2013","journal-title":"Arthritis Rheumatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"R34","DOI":"10.1186\/ar2942","article-title":"Anabolic and catabolic responses of human articular chondrocytes to varying oxygen percentages","volume":"12","author":"Strobel","year":"2010","journal-title":"Arthritis Res. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"R92","DOI":"10.1186\/ar4272","article-title":"Hypoxia promotes redifferentiation and suppresses markers of hypertrophy and degeneration in both healthy and osteoarthritic chondrocytes","volume":"15","author":"Markway","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Mennan, C., Garcia, J., McCarthy, H., Owen, S., Perry, J., Wright, K., Banerjee, R., Richardson, J.B., and Roberts, S. (2018). Human Articular Chondrocytes Retain Their Phenotype in Sustained Hypoxia While Normoxia Promotes Their Immunomodulatory Potential. Cartilage, 1947603518769714.","DOI":"10.1177\/1947603518769714"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s13287-016-0419-8","article-title":"Responses to altered oxygen tension are distinct between human stem cells of high and low chondrogenic capacity","volume":"7","author":"Anderson","year":"2016","journal-title":"Stem Cell Res. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1196\/annals.1346.009","article-title":"Hypoxia and HIF-1alpha in chondrogenesis","volume":"1068","author":"Schipani","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.1101\/gad.934301","article-title":"Hypoxia in cartilage: HIF-1alpha is essential for chondrocyte growth arrest and survival","volume":"15","author":"Schipani","year":"2001","journal-title":"Genes Dev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1002\/stem.2844","article-title":"Differential Regulation of Human Bone Marrow Mesenchymal Stromal Cell Chondrogenesis by Hypoxia Inducible Factor-1alpha Hydroxylase Inhibitors","volume":"36","author":"Taheem","year":"2018","journal-title":"Stem Cells"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"38458","DOI":"10.1074\/jbc.M406026200","article-title":"Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor","volume":"279","author":"Appelhoff","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"13041","DOI":"10.1074\/jbc.M110.211110","article-title":"Differential sensitivity of hypoxia inducible factor hydroxylation sites to hypoxia and hydroxylase inhibitors","volume":"286","author":"Tian","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.jeurceramsoc.2017.08.001","article-title":"Cobalt-containing bioactive glasses reduce human mesenchymal stem cell chondrogenic differentiation despite HIF-1\u03b1 stabilisation","volume":"38","author":"Littmann","year":"2018","journal-title":"J. Eur. Ceram. Soc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3237253","DOI":"10.1155\/2018\/3237253","article-title":"The Hypoxia-Mimetic Agent Cobalt Chloride Differently Affects Human Mesenchymal Stem Cells in Their Chondrogenic Potential","volume":"2018","author":"Teti","year":"2018","journal-title":"Stem Cells Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1111\/j.1365-2184.2009.00621.x","article-title":"Impact of oxygen environment on mesenchymal stem cell expansion and chondrogenic differentiation","volume":"42","author":"Krinner","year":"2009","journal-title":"Cell Prolif."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/scrt100","article-title":"Hypoxia mediated isolation and expansion enhances the chondrogenic capacity of bone marrow mesenchymal stromal cells","volume":"3","author":"Adesida","year":"2012","journal-title":"Stem Cell Res. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s13287-015-0075-4","article-title":"Hypoxic culture of bone marrow-derived mesenchymal stromal stem cells differentially enhances in vitro chondrogenesis within cell-seeded collagen and hyaluronic acid porous scaffolds","volume":"6","author":"Bornes","year":"2015","journal-title":"Stem Cell Res. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"241","DOI":"10.5966\/sctm.2013-0079","article-title":"Human bone marrow-derived mesenchymal stem cells display enhanced clonogenicity but impaired differentiation with hypoxic preconditioning","volume":"3","author":"Boyette","year":"2014","journal-title":"Stem Cells Transl. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.bbrc.2011.11.105","article-title":"Oxygen tension regulates the osteogenic, chondrogenic and endochondral phenotype of bone marrow derived mesenchymal stem cells","volume":"417","author":"Sheehy","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.1089\/ten.tea.2010.0661","article-title":"The influence of hypoxia and fibrinogen variants on the expansion and differentiation of adipose tissue-derived mesenchymal stem cells","volume":"17","author":"Weijers","year":"2011","journal-title":"Tissue Eng. Part A"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s40824-018-0134-x","article-title":"Hypoxic condition enhances chondrogenesis in synovium-derived mesenchymal stem cells","volume":"22","author":"Bae","year":"2018","journal-title":"Biomater. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.1089\/ten.2007.0050","article-title":"In vitro expansion of adipose-derived adult stromal cells in hypoxia enhances early chondrogenesis","volume":"13","author":"Xu","year":"2007","journal-title":"Tissue Eng."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1089\/ten.tec.2012.0142","article-title":"Recapitulating aspects of the oxygen and substrate environment of the damaged joint milieu for stem cell-based cartilage tissue engineering","volume":"19","author":"Buckley","year":"2013","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kalpakci, K.N., Brown, W.E., Hu, J.C., and Athanasiou, K.A. (2014). Cartilage tissue engineering using dermis isolated adult stem cells: The use of hypoxia during expansion versus chondrogenic differentiation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0098570"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1089\/ten.tea.2017.0235","article-title":"Articular Cartilage Repair with Mesenchymal Stem Cells After Chondrogenic Priming: A Pilot Study","volume":"24","author":"Bornes","year":"2018","journal-title":"Tissue Eng. Part A"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1089\/ten.tea.2015.0458","article-title":"Preparation of Scaffold-Free Tissue-Engineered Constructs Derived from Human Synovial Mesenchymal Stem Cells Under Low Oxygen Tension Enhances Their Chondrogenic Differentiation Capacity","volume":"22","author":"Yasui","year":"2016","journal-title":"Tissue Eng. Part A"},{"key":"ref_53","first-page":"61","article-title":"<Original Article>Hypoxia enhances proliferation through increase of colony formation rate with chondrogenic potential in primary synovial mesenchymal stem cells","volume":"63","author":"Ohara","year":"2016","journal-title":"J. Med. Dent. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1089\/ten.tec.2011.0734","article-title":"Continuous and uninterrupted oxygen tension influences the colony formation and oxidative metabolism of human mesenchymal stem cells","volume":"19","author":"Pattappa","year":"2013","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1089\/ten.tea.2010.0339","article-title":"Optimization of an in vitro three-dimensional microenvironment to reprogram synovium-derived stem cells for cartilage tissue engineering","volume":"17","author":"Li","year":"2011","journal-title":"Tissue Eng. Part A"},{"key":"ref_56","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":"ref_57","doi-asserted-by":"crossref","first-page":"2562","DOI":"10.1002\/jcp.22605","article-title":"The metabolism of human mesenchymal stem cells during proliferation and differentiation","volume":"226","author":"Pattappa","year":"2011","journal-title":"J. Cell. Physiol."},{"key":"ref_58","first-page":"15","article-title":"Oxygen effects on senescence in chondrocytes and mesenchymal stem cells: Consequences for tissue engineering","volume":"24","author":"Duwayri","year":"2004","journal-title":"Iowa Orthop. J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.bone.2006.02.061","article-title":"Low oxygen tension inhibits osteogenic differentiation and enhances stemness of human MIAMI cells","volume":"39","author":"Diabira","year":"2006","journal-title":"Bone"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1089\/scd.2015.0362","article-title":"Low Oxygen Modulates Multiple Signaling Pathways, Increasing Self-Renewal, While Decreasing Differentiation, Senescence, and Apoptosis in Stromal MIAMI Cells","volume":"25","author":"Rios","year":"2016","journal-title":"Stem Cells Dev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.bone.2005.04.040","article-title":"Hypoxia induces chondrocyte-specific gene expression in mesenchymal cells in association with transcriptional activation of Sox9","volume":"37","author":"Robins","year":"2005","journal-title":"Bone"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.3727\/096368910X564094","article-title":"Hypoxic conditions during expansion culture prime human mesenchymal stromal precursor cells for chondrogenic differentiation in three-dimensional cultures","volume":"20","author":"Muller","year":"2011","journal-title":"Cell Transplant."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1016\/j.yexcr.2009.01.020","article-title":"Transcriptional signature of human adipose tissue-derived stem cells (hASCs) preconditioned for chondrogenesis in hypoxic conditions","volume":"315","author":"Pilgaard","year":"2009","journal-title":"Exp. Cell Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"C355","DOI":"10.1152\/ajpcell.00398.2009","article-title":"Differential effects of hypoxia on osteochondrogenic potential of human adipose-derived stem cells","volume":"298","author":"Merceron","year":"2010","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.biomaterials.2005.05.071","article-title":"Chondrocytic differentiation of human adipose-derived adult stem cells in elastin-like polypeptide","volume":"27","author":"Betre","year":"2006","journal-title":"Biomaterials"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"C1139","DOI":"10.1152\/ajpcell.00415.2005","article-title":"Effect of reduced oxygen tension on chondrogenesis and osteogenesis in adipose-derived mesenchymal cells","volume":"290","author":"Malladi","year":"2006","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4266","DOI":"10.1016\/j.biomaterials.2013.02.064","article-title":"The effect of hypoxia on the chondrogenic differentiation of co-cultured articular chondrocytes and mesenchymal stem cells in scaffolds","volume":"34","author":"Meretoja","year":"2013","journal-title":"Biomaterials"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Desance, M., Contentin, R., Bertoni, L., Gomez-Leduc, T., Branly, T., Jacquet, S., Betsch, J.M., Batho, A., Legendre, F., and Audigie, F. (2018). Chondrogenic Differentiation of Defined Equine Mesenchymal Stem Cells Derived from Umbilical Cord Blood for Use in Cartilage Repair Therapy. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020537"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Gomez-Leduc, T., Desance, M., Hervieu, M., Legendre, F., Ollitrault, D., de Vienne, C., Herlicoviez, M., Galera, P., and Demoor, M. (2017). Hypoxia Is a Critical Parameter for Chondrogenic Differentiation of Human Umbilical Cord Blood Mesenchymal Stem Cells in Type I\/III Collagen Sponges. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18091933"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s00441-013-1732-5","article-title":"Hypoxia enhances chondrogenic differentiation of human adipose tissue-derived stromal cells in scaffold-free and scaffold systems","volume":"355","author":"Munir","year":"2014","journal-title":"Cell Tissue Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1002\/jcp.20324","article-title":"Influence of oxygen on the proliferation and metabolism of adipose derived adult stem cells","volume":"204","author":"Wang","year":"2005","journal-title":"J. Cell. Physiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"R55","DOI":"10.1186\/ar2211","article-title":"Hypoxic conditions increase hypoxia-inducible transcription factor 2\u03b1 and enhance chondrogenesis in stem cells from the infrapatellar fat pad of osteoarthritis patients","volume":"9","author":"Khan","year":"2007","journal-title":"Arthritis Res. Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1089\/ten.2006.0265","article-title":"Hypoxia inducible factor-1alpha deficiency affects chondrogenesis of adipose-derived adult stromal cells","volume":"13","author":"Malladi","year":"2007","journal-title":"Tissue Eng."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1016\/j.joca.2009.04.023","article-title":"Hypoxia reduces the inhibitory effect of IL-1\u03b2 on chondrogenic differentiation of FCS-free expanded MSC","volume":"17","author":"Felka","year":"2009","journal-title":"Osteoarthr. Cartil."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1002\/jbm.a.32577","article-title":"Human mesenchymal stem cells: Influence of oxygen pressure on proliferation and chondrogenic differentiation in fibrin glue in vitro","volume":"93","author":"Baumgartner","year":"2010","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1016\/j.joca.2010.07.004","article-title":"Oxygen tension differentially regulates the functional properties of cartilaginous tissues engineered from infrapatellar fat pad derived MSCs and articular chondrocytes","volume":"18","author":"Buckley","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1002\/jor.21043","article-title":"Bone marrow-derived mesenchymal stem cells express the pericyte marker 3G5 in culture and show enhanced chondrogenesis in hypoxic conditions","volume":"28","author":"Khan","year":"2010","journal-title":"J. Orthop. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2516","DOI":"10.1016\/j.jbiomech.2010.05.020","article-title":"Low oxygen tension is a more potent promoter of chondrogenic differentiation than dynamic compression","volume":"43","author":"Meyer","year":"2010","journal-title":"J. Biomech."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"533","DOI":"10.22203\/eCM.v021a40","article-title":"Role of hypoxia and growth and differentiation factor-5 on differentiation of human mesenchymal stem cells towards intervertebral nucleus pulposus-like cells","volume":"21","author":"Stoyanov","year":"2011","journal-title":"Eur. Cell Mater."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1089\/ten.tea.2011.0657","article-title":"Hypoxia impedes hypertrophic chondrogenesis of human multipotent stromal cells","volume":"18","author":"Gawlitta","year":"2012","journal-title":"Tissue Eng. Part A"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Portron, S., Merceron, C., Gauthier, O., Lesoeur, J., Sourice, S., Masson, M., Fellah, B.H., Geffroy, O., Lallemand, E., and Weiss, P. (2013). Effects of in vitro low oxygen tension preconditioning of adipose stromal cells on their in vivo chondrogenic potential: Application in cartilage tissue repair. PLoS ONE, 8.","DOI":"10.1530\/boneabs.1.PP255"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"13954","DOI":"10.1073\/pnas.1410977111","article-title":"Metabolic programming of mesenchymal stromal cells by oxygen tension directs chondrogenic cell fate","volume":"111","author":"Leijten","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1016\/j.actbio.2013.12.015","article-title":"Differential effect of hypoxia on human mesenchymal stem cell chondrogenesis and hypertrophy in hyaluronic acid hydrogels","volume":"10","author":"Zhu","year":"2014","journal-title":"Acta Biomater."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1159\/000369742","article-title":"Inverse regulation of early and late chondrogenic differentiation by oxygen tension provides cues for stem cell-based cartilage tissue engineering","volume":"35","author":"Portron","year":"2015","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"425","DOI":"10.22203\/eCM.v031a27","article-title":"Reoxygenation enhances tumour necrosis factor alpha-induced degradation of the extracellular matrix produced by chondrogenic cells","volume":"31","author":"Markway","year":"2016","journal-title":"Eur. Cell Mater."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1177\/1947603516659344","article-title":"Molecular Validation of Chondrogenic Differentiation and Hypoxia Responsiveness of Platelet-Lysate Expanded Adipose Tissue-Derived Human Mesenchymal Stromal Cells","volume":"8","author":"Camilleri","year":"2017","journal-title":"Cartilage"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3406","DOI":"10.1038\/s41598-017-03579-y","article-title":"Enhanced chondrogenesis of bone marrow-derived stem cells by using a combinatory cell therapy strategy with BMP-2\/TGF-beta1, hypoxia, and COL1A1\/HtrA1 siRNAs","volume":"7","author":"Legendre","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1002\/jbm.a.36043","article-title":"Influence of oxygen levels on chondrogenesis of porcine mesenchymal stem cells cultured in polycaprolactone scaffolds","volume":"105","author":"Kelly","year":"2017","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1634\/stemcells.2006-0398","article-title":"Transcriptional profiling of human cord blood CD133+ and cultured bone marrow mesenchymal stem cells in response to hypoxia","volume":"25","author":"Hale","year":"2007","journal-title":"Stem Cells"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"29","DOI":"10.3727\/096368909X478560","article-title":"Enhanced chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells in low oxygen environment micropellet cultures","volume":"19","author":"Markway","year":"2010","journal-title":"Cell Transplant."},{"key":"ref_91","first-page":"145","article-title":"Chondrogenic potential of bone marrow- and adipose tissue-derived adult human mesenchymal stem cells","volume":"20","author":"Ronziere","year":"2010","journal-title":"Biomed. Mater. Eng."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"6042","DOI":"10.1016\/j.biomaterials.2012.04.061","article-title":"Molecular mechanism of hypoxia-induced chondrogenesis and its application in in vivo cartilage tissue engineering","volume":"33","author":"Duval","year":"2012","journal-title":"Biomaterials"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2683","DOI":"10.1038\/srep02683","article-title":"Hypoxia enhances chondrogenesis and prevents terminal differentiation through PI3K\/Akt\/FoxO dependent anti-apoptotic effect","volume":"3","author":"Lee","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.tvjl.2012.06.008","article-title":"Expansion under hypoxic conditions enhances the chondrogenic potential of equine bone marrow-derived mesenchymal stem cells","volume":"195","author":"Ranera","year":"2013","journal-title":"Vet. J."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1089\/ten.tea.2016.0426","article-title":"Hypoxia for Mesenchymal Stem Cell Expansion and Differentiation: The Best Way for Enhancing TGFss-Induced Chondrogenesis and Preventing Calcifications in Alginate Beads","volume":"23","author":"Henrionnet","year":"2017","journal-title":"Tissue Eng. Part A"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1089\/ten.tea.2016.0270","article-title":"Hypoxic Expansion of Human Mesenchymal Stem Cells Enhances Three-Dimensional Maturation of Tissue-Engineered Intervertebral Discs","volume":"23","author":"Hudson","year":"2017","journal-title":"Tissue Eng. Part A"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.scr.2018.01.010","article-title":"Enhancing proliferation and optimizing the culture condition for human bone marrow stromal cells using hypoxia and fibroblast growth factor-2","volume":"28","author":"Lee","year":"2018","journal-title":"Stem Cell Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1089\/ten.tea.2011.0575","article-title":"The role of environmental factors in regulating the development of cartilaginous grafts engineered using osteoarthritic human infrapatellar fat pad-derived stem cells","volume":"18","author":"Liu","year":"2012","journal-title":"Tissue Eng. Part A"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Pattappa, G.S.R., Hofmeister, I., Seja, J., Zellner, J., Johnstone, B., Docheva, D., and Angele, P. (2018). Physioxia has a beneficial effect on cartilage matrix production in interleukin-1\u03b2 inhibited mesenchymal stem cell chondrogenesis. Stem Cells Int., in submit.","DOI":"10.3390\/cells8080936"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1002\/jcp.21965","article-title":"Population doublings and percentage of S100-positive cells as predictors of in vitro chondrogenicity of expanded human articular chondrocytes","volume":"222","author":"Giovannini","year":"2010","journal-title":"J. Cell. Physiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3020","DOI":"10.1002\/art.22840","article-title":"Interleukin-1\u03b2 impairment of transforming growth factor \u03b21 signaling by down-regulation of transforming growth factor beta receptor type II and up-regulation of Smad7 in human articular chondrocytes","volume":"56","author":"Bauge","year":"2007","journal-title":"Arthritis Rheumatol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/art.23154","article-title":"Interleukin-1beta up-regulation of Smad7 via NF-\u03baB activation in human chondrocytes","volume":"58","author":"Bauge","year":"2008","journal-title":"Arthritis Rheumatol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1111\/j.1582-4934.2007.00173.x","article-title":"NF\u03baB mediates IL-1\u03b2-induced down-regulation of T\u03b2RII through the modulation of Sp3 expression","volume":"12","author":"Bauge","year":"2008","journal-title":"J. Cell. Mol. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s00264-004-0618-2","article-title":"Hypoxia and HIF-1\u03b1 in osteoarthritis","volume":"29","author":"Pfander","year":"2005","journal-title":"Int. Orthop."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s00441-009-0841-7","article-title":"Extracellular matrix genes as hypoxia-inducible targets","volume":"339","author":"Myllyharju","year":"2010","journal-title":"Cell Tissue Res."},{"key":"ref_106","first-page":"2800","article-title":"Hypoxia-Inducible Factors (HIFs) in the articular cartilage: A systematic review","volume":"21","year":"2017","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/nm.2153","article-title":"Hypoxia-inducible factor-2\u03b1 is a catabolic regulator of osteoarthritic cartilage destruction","volume":"16","author":"Yang","year":"2010","journal-title":"Nat. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1016\/j.joca.2010.10.006","article-title":"HIF-2\u03b1 as a possible therapeutic target of osteoarthritis","volume":"18","author":"Saito","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.joca.2003.12.005","article-title":"Hypoxia inducible factor-1\u03b1 expression in human normal and osteoarthritic chondrocytes","volume":"12","author":"Coimbra","year":"2004","journal-title":"Osteoarthr. Cartil."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/nm.2146","article-title":"Transcriptional regulation of endochondral ossification by HIF-2\u03b1 during skeletal growth and osteoarthritis development","volume":"16","author":"Saito","year":"2010","journal-title":"Nat. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2732","DOI":"10.1002\/art.30451","article-title":"Interleukin-6 plays an essential role in hypoxia-inducible factor 2\u03b1-induced experimental osteoarthritic cartilage destruction in mice","volume":"63","author":"Ryu","year":"2011","journal-title":"Arthritis Rheumatol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/nm0111-25","article-title":"Lack of HIF-2\u03b1 in limb bud mesenchyme causes a modest and transient delay of endochondral bone development","volume":"17","author":"Araldi","year":"2011","journal-title":"Nat. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1002\/jor.22063","article-title":"A large-scale replication study for the association of rs17039192 in HIF-2\u03b1 with knee osteoarthritis","volume":"30","author":"Nakajima","year":"2012","journal-title":"J. Orthop. Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1038\/cr.2010.99","article-title":"HIF-2\u03b1\u2014A mediator of osteoarthritis?","volume":"20","author":"Murphy","year":"2010","journal-title":"Cell Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1007\/s00441-011-1193-7","article-title":"Effects of oxygen and culture system on in vitro propagation and redifferentiation of osteoarthritic human articular chondrocytes","volume":"347","author":"Schrobback","year":"2012","journal-title":"Cell Tissue Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"176ra134","DOI":"10.1126\/scitranslmed.3005409","article-title":"Proteoglycan 4 expression protects against the development of osteoarthritis","volume":"5","author":"Ruan","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1002\/jor.22930","article-title":"Hypoxia-inducible factor 3-\u03b1 expression is associated with the stable chondrocyte phenotype","volume":"33","author":"Markway","year":"2015","journal-title":"J. Orthop. Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41413-018-0021-z","article-title":"The art of building bone: Emerging role of chondrocyte-to-osteoblast transdifferentiation in endochondral ossification","volume":"6","author":"Aghajanian","year":"2018","journal-title":"Bone Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1038\/ncb3067","article-title":"A subset of chondrogenic cells provides early mesenchymal progenitors in growing bones","volume":"16","author":"Ono","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/j.1749-6632.1990.tb42363.x","article-title":"Hypertrophic chondrocytes. The terminal stage of differentiation in the chondrogenic cell lineage?","volume":"599","author":"Pacifici","year":"1990","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1111\/j.1365-2443.2008.01209.x","article-title":"PI3K\/Akt signaling as a key regulatory pathway for chondrocyte terminal differentiation","volume":"13","author":"Kita","year":"2008","journal-title":"Genes Cells"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1002\/jcb.22604","article-title":"Biology and pathology of Rho GTPase, PI-3 kinase-Akt, and MAP kinase signaling pathways in chondrocytes","volume":"110","author":"Beier","year":"2010","journal-title":"J. Cell. Biochem."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.joca.2013.11.004","article-title":"Dysregulated FOXO transcription factors in articular cartilage in aging and osteoarthritis","volume":"22","author":"Akasaki","year":"2014","journal-title":"Osteoarthr. Cartil."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Matsuzaki, T., Alvarez-Garcia, O., Mokuda, S., Nagira, K., Olmer, M., Gamini, R., Miyata, K., Akasaki, Y., Su, A.I., and Asahara, H. (2018). FoxO transcription factors modulate autophagy and proteoglycan 4 in cartilage homeostasis and osteoarthritis. Sci. Transl. Med., 10.","DOI":"10.1126\/scitranslmed.aan0746"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.febslet.2007.11.025","article-title":"The FoxO transcription factors and metabolic regulation","volume":"582","author":"Nakae","year":"2008","journal-title":"FEBS Lett."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/nrm2190","article-title":"Stressing the role of FoxO proteins in lifespan and disease","volume":"8","author":"Burgering","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1002\/art.27305","article-title":"Autophagy is a protective mechanism in normal cartilage, and its aging-related loss is linked with cell death and osteoarthritis","volume":"62","author":"Carames","year":"2010","journal-title":"Arthritis Rheumatol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/nrrheum.2011.109","article-title":"Autophagy and cartilage homeostasis mechanisms in joint health, aging and OA","volume":"7","author":"Lotz","year":"2011","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"76","DOI":"10.3389\/fbioe.2017.00076","article-title":"Dynamic Mechanical Compression of Chondrocytes for Tissue Engineering: A Critical Review","volume":"5","author":"Anderson","year":"2017","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.jbiomech.2009.09.018","article-title":"Mechanics and mechanobiology of mesenchymal stem cell-based engineered cartilage","volume":"43","author":"Huang","year":"2010","journal-title":"J. Biomech."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/scrt211","article-title":"Mechanical regulation of chondrogenesis","volume":"4","author":"Case","year":"2013","journal-title":"Stem Cell Res. Ther."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1114\/1.239","article-title":"Interstitial fluid pressurization during confined compression cyclical loading of articular cartilage","volume":"28","author":"Soltz","year":"2000","journal-title":"Ann. Biomed. Eng."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/S0021-9290(98)00105-5","article-title":"Experimental verification and theoretical prediction of cartilage interstitial fluid pressurization at an impermeable contact interface in confined compression","volume":"31","author":"Soltz","year":"1998","journal-title":"J. Biomech."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.jbiomech.2014.01.002","article-title":"Mechanobiological simulations of prenatal joint morphogenesis","volume":"47","author":"Giorgi","year":"2014","journal-title":"J. Biomech."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1098\/rstb.2003.1346","article-title":"Modelling cartilage mechanobiology","volume":"358","author":"Carter","year":"2003","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s00441-016-2512-9","article-title":"Chondrogenesis of embryonic limb bud cells in micromass culture progresses rapidly to hypertrophy and is modulated by hydrostatic pressure","volume":"368","author":"Saha","year":"2017","journal-title":"Cell Tissue Res."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"121","DOI":"10.22203\/eCM.v023a09","article-title":"Hydrostatic pressure acts to stabilise a chondrogenic phenotype in porcine joint tissue derived stem cells","volume":"23","author":"Vinardell","year":"2012","journal-title":"Eur. Cell Mater."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.1089\/ten.tea.2008.0672","article-title":"The effect of hydrostatic pressure on three-dimensional chondroinduction of human adipose-derived stem cells","volume":"15","author":"Ogawa","year":"2009","journal-title":"Tissue Eng. Part A"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1089\/ten.tea.2013.0525","article-title":"Hydrostatic pressure-driven three-dimensional cartilage induction using human adipose-derived stem cells and collagen gels","volume":"21","author":"Ogawa","year":"2015","journal-title":"Tissue Eng. Part A"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1002\/jcp.21890","article-title":"p38 MAPK mediated in compressive stress-induced chondrogenesis of rat bone marrow MSCs in 3D alginate scaffolds","volume":"221","author":"Li","year":"2009","journal-title":"J. Cell. Physiol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"3050","DOI":"10.1089\/ten.tea.2014.0035","article-title":"Infrapatellar fat pad-derived stem cells maintain their chondrogenic capacity in disease and can be used to engineer cartilaginous grafts of clinically relevant dimensions","volume":"20","author":"Liu","year":"2014","journal-title":"Tissue Eng. Part A"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1016\/j.actbio.2012.03.016","article-title":"Cell-matrix interactions regulate mesenchymal stem cell response to hydrostatic pressure","volume":"8","author":"Steward","year":"2012","journal-title":"Acta Biomater."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1016\/j.joca.2011.07.005","article-title":"Structured three-dimensional co-culture of mesenchymal stem cells with chondrocytes promotes chondrogenic differentiation without hypertrophy","volume":"19","author":"Cooke","year":"2011","journal-title":"Osteoarthr. Cartil."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1002\/jcp.22706","article-title":"Enhanced chondrocyte proliferation and mesenchymal stromal cells chondrogenesis in coculture pellets mediate improved cartilage formation","volume":"227","author":"Acharya","year":"2012","journal-title":"J. Cell. Physiol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/978-1-4939-1619-1_4","article-title":"Engineering cartilage tissue by pellet coculture of chondrocytes and mesenchymal stromal cells","volume":"1226","author":"Wu","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.devcel.2012.03.011","article-title":"FoxA family members are crucial regulators of the hypertrophic chondrocyte differentiation program","volume":"22","author":"Ionescu","year":"2012","journal-title":"Dev. Cell"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"D447","DOI":"10.1093\/nar\/gku1003","article-title":"STRING v10: Protein-protein interaction networks, integrated over the tree of life","volume":"43","author":"Szklarczyk","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1002\/term.1744","article-title":"FGF, TGF\u03b2 and Wnt crosstalk: Embryonic to in vitro cartilage development from mesenchymal stem cells","volume":"9","author":"Cleary","year":"2015","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Williams, R., Khan, I.M., Richardson, K., Nelson, L., McCarthy, H.E., Analbelsi, T., Singhrao, S.K., Dowthwaite, G.P., Jones, R.E., and Baird, D.M. (2010). Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013246"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.tvjl.2011.08.036","article-title":"The comparison of equine articular cartilage progenitor cells and bone marrow-derived stromal cells as potential cell sources for cartilage repair in the horse","volume":"192","author":"McCarthy","year":"2012","journal-title":"Vet. J."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1177\/1947603514544953","article-title":"Evidence of a Viable Pool of Stem Cells within Human Osteoarthritic Cartilage","volume":"5","author":"Nelson","year":"2014","journal-title":"Cartilage"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1242\/jcs.00912","article-title":"The surface of articular cartilage contains a progenitor cell population","volume":"117","author":"Dowthwaite","year":"2004","journal-title":"J. Cell Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/3\/484\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:28:10Z","timestamp":1760185690000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/3\/484"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,23]]},"references-count":152,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,2]]}},"alternative-id":["ijms20030484"],"URL":"https:\/\/doi.org\/10.3390\/ijms20030484","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,23]]}}}