Investigating the role of tenomodulin in tendon healing using tenomodulin knockout model

• Applicant: Professorin Dr. Denitsa Docheva, Ph.D.
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2014 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 260210937

Tendons and ligaments, the force-transmitting tissues of the musculoskeletal system, are prone to age-related degeneration and subsequent traumatic ruptures, a dominant burden in orthopaedic medicine that is further amplified due to their poor tissue healing. Tenomodulin (Tnmd), a novel type of protein, is predominantly expressed in tendons and ligaments; hence it is currently the best-known gene marker for these tissues. We have generated Tnmd knockout mouse strain and our analysis revealed that Tnmd is a regulatory factor in tendon cell adhesion and proliferation as well as collagen fibril maturation; processes that are also fundamental during tendon repair. Furthermore, we have found that the loss of Tnmd expression is directly associated to the predisposition of heart tendons to rupture. Despite its anticipated importance, our knowledge about the role of Tnmd in tendon pathophysiology and repair is limited. Thus, the primary purpose of this proposal is to gain mechanistic insights into the function of Tnmd in tendon healing. To achieve this aim, Tnmd-deficient mice will be examined in 1) surgically induced rupture model of Achilles tendon, 2) macro and nano biomechanical tests; 3) mouse running exercises and 4) in vitro analyses of Tnmd RNA and protein forms and comparison of mouse and human tendon-derived cells. These complementary experimental approaches will provide a better understanding of tendon repair and function, and may identify Tnmd as a novel target for the development of tendon-specific therapeutic drugs.

• DFG Programme: Research Grants
• Participating Persons: Professor Dr. Hauke Clausen-Schaumann; Professor Dr. Peter Müller