Tenomodulin knockout mice exhibit worse late healing outcomes with augmented trauma-induced heterotopic ossification of Achilles tendon.
Manuel Delgado Caceres, Katharina Angerpointner, Michael Galler, Dasheng Lin, Philipp A Michel, Christoph Brochhausen, Xin Lu, Adithi R Varadarajan, Jens Warfsmann, Richard Stange, Volker Alt, Christian G Pfeifer, Denitsa Docheva
Cell death & disease 2021 Nov 05Heterotopic ossification (HO) represents a common problem after tendon injury with no effective treatment yet being developed. Tenomodulin (Tnmd), the best-known mature marker for tendon lineage cells, has important effects in tendon tissue aging and function. We have reported that loss of Tnmd leads to inferior early tendon repair characterized by fibrovascular scaring and therefore hypothesized that its lack will persistently cause deficient repair during later stages. Tnmd knockout (Tnmd-/-) and wild-type (WT) animals were subjected to complete Achilles tendon surgical transection followed by end-to-end suture. Lineage tracing revealed a reduction in tendon-lineage cells marked by ScleraxisGFP, but an increase in alpha smooth muscle actin myofibroblasts in Tnmd-/- tendon scars. At the proliferative stage, more pro-inflammatory M1 macrophages and larger collagen II cartilaginous template were detected in this group. At the remodeling stage, histological scoring revealed lower repair quality in the injured Tnmd-/- tendons, which was coupled with higher HO quantified by micro-CT. Tendon biomechanical properties were compromised in both groups upon injury, however we identified an abnormal stiffening of non-injured Tnmd-/- tendons, which possessed higher static and dynamic E-moduli. Pathologically thicker and abnormally shaped collagen fibrils were observed by TEM in Tnmd-/- tendons and this, together with augmented HO, resulted in diminished running capacity of Tnmd-/- mice. These novel findings demonstrate that Tnmd plays a protecting role against trauma-induced endochondral HO and can inspire the generation of novel therapeutics to accelerate repair. © 2021. The Author(s).
Citation
Manuel Delgado Caceres, Katharina Angerpointner, Michael Galler, Dasheng Lin, Philipp A Michel, Christoph Brochhausen, Xin Lu, Adithi R Varadarajan, Jens Warfsmann, Richard Stange, Volker Alt, Christian G Pfeifer, Denitsa Docheva. Tenomodulin knockout mice exhibit worse late healing outcomes with augmented trauma-induced heterotopic ossification of Achilles tendon. Cell death & disease. 2021 Nov 05;12(11):1049
Mesh Tags
Substances
PMID: 34741033
View Full Text
