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When we cultured BMSCs in the chip and implanted them into the rabbit defect models of low-oxygen cartilage and high-oxygen calvaria bone, (i) the low oxygen level (base) promoted stemness and chondrogenesis of BMSCs with robust antioxidative potential; (ii) the middle level (two times \u2265 low) pushed BMSCs to quiescence; and (iii) the high level (four times \u2265 low) promoted osteogenesis by disturbing the redox balance and stemness. Last, endochondral or intramembranous osteogenesis upon transition from low to high oxygen in vivo suggests a developmental mechanism\u2013driven solution to promote chondrogenesis to osteogenesis in the skeletal system by regulating the oxygen environment.<\/jats:p>","DOI":"10.1126\/sciadv.add4210","type":"journal-article","created":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T18:01:34Z","timestamp":1679508094000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":8,"title":["O\n            <sub>2<\/sub>\n            variant chip to simulate site-specific skeletogenesis from hypoxic bone marrow"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5965-7205","authenticated-orcid":true,"given":"Hye-Seon","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Medical Engineering, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, 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