Conditional tenomodulin overexpression favors tenogenic lineage differentiation of transgenic mouse derived cells

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.