title: Characterization of BMP signaling dependent osteogenesis using a BMP depletable avianized bone marrow stromal cell line (TVA-BMSC).
abstract: Adipogenesis, chondrogenesis and osteogenesis are BMP signaling dependent differentiation processes. However, the molecular networks operating downstream of BMP signaling to bring about these distinct fates are yet to be fully elucidated. We have developed a novel Bone Marrow Stromal Cell (BMSC) derived mouse cell line as a powerful in vitro platform to conduct such experiments. This cell line is a derivative of BMSCs isolated from a tamoxifen inducible Bmp2 and Bmp4 double conditional knock-out mouse strain. These BMSCs are immortalized and stably transfected with avian retroviral receptor TVA (TVA-BMSCs), enabling an easy method for stable transduction of multiple genes in these cells. In TVA-BMSCs multiple components of BMP signaling pathway can be manipulated simultaneously. Using this cell line we have demonstrated that for osteogenesis, BMP signaling is required only for the first three days. We have further demonstrated that Klf10, an osteogenic transcription factor which is transcribed in developing bones in a BMP signaling dependent manner, can largely compensate for the loss of BMP signaling during osteogenesis of BMSCs. TVA-BMSCs can undergo chondrogenesis and adipogenesis, and hence may be used for dissection of the molecular networks downstream of BMP signaling in these differentiation processes as well.
authors.affiliation: Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, Uttar Pradesh 208016, India.
authors.forename: Prem Swaroop
authors.initials: PS
authors.lastname: Yadav
authors.affiliation: Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, Uttar Pradesh 208016, India.
authors.forename: Mohd Parvez
authors.initials: MP
authors.lastname: Khan
authors.affiliation: Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, Uttar Pradesh 208016, India.
authors.forename: Paritosh
authors.initials: P
authors.lastname: Prashar
authors.affiliation: Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, Uttar Pradesh 208016, India.
authors.forename: Shivali
authors.initials: S
authors.lastname: Duggal
authors.affiliation: Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, Uttar Pradesh 208016, India.
authors.forename: Srikanta Kumar
authors.initials: SK
authors.lastname: Rath
authors.affiliation: Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, Uttar Pradesh 208016, India.
authors.forename: Naibedya
authors.initials: N
authors.lastname: Chattopadhyay
authors.affiliation: Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, Uttar Pradesh 208016, India. Electronic address: abandopa@iitk.ac.in.
authors.forename: Amitabha
authors.initials: A
authors.lastname: Bandyopadhyay
mesh_terms: D050156:Adipogenesis; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D001861:Bone Regeneration; D002460:Cell Line; D002645:Chickens; D020219:Chondrogenesis; D051765:Early Growth Response Transcription Factors / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D010012:Osteogenesis; D015398:Signal Transduction; D000076182:Sp7 Transcription Factor / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D051765:Early Growth Response Transcription Factors; C569958:KLF10 protein, mouse; D051741:Kruppel-Like Transcription Factors; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse
keywords: Adipocytes; BMP signaling; BMSC; Bone; Cartilage; Chondrogenesis; Klf10; Osteogenesis; Osx; Runx2