title: Conditional tenomodulin overexpression favors tenogenic lineage differentiation of transgenic mouse derived cells.
abstract: Tenomodulin (TNMD) is a type II transmembrane protein that is widely expressed in a variety of avascular connective tissues and fat tissue. Its function remains largely unknown except for a marker for mature tenocytes. This study reports the generation of tetracycline (Tet)-on driven conditional TNMD overexpressing mice and thus to provide a tool for systemic investigation of its role in regulating functions of various tissues. The current study focuses on in vitro comparison of tenogenic differentiation potentials induced by doxycycline (Dox) treatment among bone marrow derived stem cells (BMSCs), adipose derived stem cells (ASCs), dermal fibroblasts (DFs) and tenocytes (TCs) of the same transgenic mice. The results showed that BMSCs exhibited the best tenogenic potential than other three cell types (p<0.05 for majority of markers), whereas ASCs and DFs revealed similar potentials (p>0.05 for majority of markers). TCs were found the least capable of being induced for tenogenic gene expression. In addition, TNMD overexpression also significantly inhibited the differentiation towards osteogenic and chondrogenic lineages in both BMSCs and ASCs (p<0.05). However, the inhibition of adipogenic differentiation was not observed in ASCs (p>0.05), suggesting different gene regulation mechanisms may involve in different tissue types and thus leading to different functions, which is likely to be revealed with a transgenic mouse model.
authors: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, 639 ZhiZaoJu Road, Shanghai 200011, PR China.
authors: Yuan
authors: Y
authors: Shi
authors: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, 639 ZhiZaoJu Road, Shanghai 200011, PR China.
authors: Yao
authors: Y
authors: Xiong
authors: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, 639 ZhiZaoJu Road, Shanghai 200011, PR China.
authors: Yongkang
authors: Y
authors: Jiang
authors: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, 639 ZhiZaoJu Road, Shanghai 200011, PR China; National Tissue Engineering Center of China, Shanghai, PR China.
authors: Zhiyong
authors: Z
authors: Zhang
authors: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, 639 ZhiZaoJu Road, Shanghai 200011, PR China; National Tissue Engineering Center of China, Shanghai, PR China.
authors: Guangdong
authors: G
authors: Zhou
authors: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, 639 ZhiZaoJu Road, Shanghai 200011, PR China; National Tissue Engineering Center of China, Shanghai, PR China.
authors: Wenjie
authors: W
authors: Zhang
authors: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, 639 ZhiZaoJu Road, Shanghai 200011, PR China; National Tissue Engineering Center of China, Shanghai, PR China.
authors: Yilin
authors: Y
authors: Cao
authors: Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200092, PR China. Electronic address: hejing76@126.com.
authors: Jing
authors: J
authors: He
authors: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, 639 ZhiZaoJu Road, Shanghai 200011, PR China; National Tissue Engineering Center of China, Shanghai, PR China. Electronic address: liuwei_2000@yahoo.com.
authors: Wei
authors: W
authors: Liu
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013710:Tendons / Q000166:cytology* / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D008565:Membrane Proteins; C486026:Tnmd protein, mouse
keywords: Conditional overexpressing transgenic mice; MSCs; Multi-lineage differentiation; TNMD overexpression; Tenogenic differentiation