title: BMP2 induces chondrogenic differentiation, osteogenic differentiation and endochondral ossification in stem cells.
abstract: Bone morphogenetic protein 2 (BMP2), a member of the transforming growth factor-β (TGF-β) super-family, is one of the main chondrogenic growth factors involved in cartilage regeneration. BMP2 is known to induce chondrogenic differentiation in various types of stem cells in vitro. However, BMP2 also induces osteogenic differentiation and endochondral ossification in mesenchymal stem cells (MSCs). Although information regarding BMP2-induced chondrogenic and osteogenic differentiation within the same system might be essential for cartilage tissue engineering, few studies concerning these issues have been conducted. In this study, BMP2 was identified as a regulator of chondrogenic differentiation, osteogenic differentiation and endochondral bone formation within the same system. BMP2 was used to regulate chondrogenic and osteogenic differentiation in stem cells within the same culture system in vitro and in vivo. Any changes in the differentiation markers were assessed. BMP2 was found to induce chondrogenesis and osteogenesis in vitro via the expression of Sox9, Runx2 and its downstream markers. According to the results of the subcutaneous stem cell implantation studies, BMP2 not only induced cartilage formation but also promoted endochondral ossification during ectopic bone/cartilage formation. In fetal limb cultures, BMP2 promoted chondrocyte hypertrophy and endochondral ossification. Our data reveal that BMP2 can spontaneously induce chondrogenic differentiation, osteogenic differentiation and endochondral bone formation within the same system. Thus, BMP2 can be used in cartilage tissue engineering to regulate cartilage formation but has to be properly regulated for cartilage tissue engineering in order to retain the cartilage phenotype.
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.
authors.forename: Nian
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Hu
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.
authors.forename: Jun-Yi
authors.initials: JY
authors.lastname: Liao
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.
authors.forename: Liang-Bo
authors.initials: LB
authors.lastname: Lin
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.
authors.forename: Zhen-Ming
authors.initials: ZM
authors.lastname: Hu
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China. huangwei68@263.net.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001846:Bone Development; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D002454:Cell Differentiation; D019902:Chondrocytes / Q000473:pathology; D020219:Chondrogenesis; D003094:Collagen / Q000378:metabolism; D005121:Extremities / Q000196:embryology; D005333:Fetus / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D006984:Hypertrophy; D051379:Mice; D010012:Osteogenesis; D013194:Staining and Labeling; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: C525718:BMP2 protein, human; D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; D049452:Green Fluorescent Proteins; D003094:Collagen
keywords: Bone morphogenetic protein 2; Cartilage tissue engineering; Chondrogenic differentiation; Osteogenic differentiation; Stem cell