title: Sox9 potentiates BMP2-induced chondrogenic differentiation and inhibits BMP2-induced osteogenic differentiation.
abstract: Bone morphogenetic protein 2 (BMP2) is one of the key chondrogenic growth factors involved in the cartilage regeneration. However, it also exhibits osteogenic abilities and triggers endochondral ossification. Effective chondrogenesis and inhibition of BMP2-induced osteogenesis and endochondral ossification can be achieved by directing the mesenchymal stem cells (MSCs) towards chondrocyte lineage with chodrogenic factors, such as Sox9. Here we investigated the effects of Sox9 on BMP2-induced chondrogenic and osteogenic differentiation of MSCs. We found exogenous overexpression of Sox9 enhanced the BMP2-induced chondrogenic differentiation of MSCs in vitro. Also, it inhibited early and late osteogenic differentiation of MSCs in vitro. Subcutaneous stem cell implantation demonstrated Sox9 potentiated BMP2-induced cartilage formation and inhibited endochondral ossification. Mouse limb cultures indicated that BMP2 and Sox9 acted synergistically to stimulate chondrocytes proliferation, and Sox9 inhibited BMP2-induced chondrocytes hypertrophy and ossification. This study strongly suggests that Sox9 potentiates BMP2-induced MSCs chondrogenic differentiation and cartilage formation, and inhibits BMP2-induced MSCs osteogenic differentiation and endochondral ossification. Thus, exogenous overexpression of Sox9 in BMP2-induced mesenchymal stem cells differentiation may be a new strategy for cartilage tissue engineering.
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Junyi
authors.initials: J
authors.lastname: Liao
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Hu
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Nian
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Liangbo
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Shixiong
authors.initials: S
authors.lastname: Yi
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Tingxu
authors.initials: T
authors.lastname: Fan
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Bao
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Yongming
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Clinical Hematology, Third Military Medical University, Chongqing, China.
authors.forename: Weike
authors.initials: W
authors.lastname: Si
authors.affiliation: Department of Clinical Hematology, Third Military Medical University, Chongqing, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics* / Q000378:metabolism; D002356:Cartilage / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D020219:Chondrogenesis / Q000235:genetics*; D015870:Gene Expression; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D010011:Osteocytes / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics; D055758:SOX9 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D023822:Tissue Engineering; D019076:Transgenes
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse