Tenomodulin and Chondromodulin-1 Are Both Required to Maintain Biomechanical Function and Prevent Intervertebral Disc Degeneration.

Theodor Di Pauli von Treuheim, Olivia M Torre, Emily D Ferreri, Philip Nasser, Angelica Abbondandolo, Manuel Delgado Caceres, Dasheng Lin, Denitsa Docheva, James C Iatridis

Cartilage 2021 Dec

filter terms:

The underlying mechanisms and molecular factors influencing intervertebral disc (IVD) homeostasis and degeneration remain clinically relevant. Tenomodulin (Tnmd) and chondromodulin (Chm1) are antiangiogenic transmembrane glycoproteins, with cleavable C-terminus, expressed by IVD cells that are implicated in the onset of degenerative processes. We evaluate the organ-level biomechanical impact of knocking out Tnmd alone, and Tnmd and Chm1, simultaneously. Caudal (c5-8) and lumbar vertebrae (L1-4) of skeletally mature male and female 9-month-old wildtype (WT), Tnmd knockout (Tnmd-/-), and Tnmd/Chm1 double knockout (Tnmd-/-/Chm-/-) mice were used (n = 9-13 per group). Disc height index (DHI), histomorphological changes, and axial, torsional, creep, and failure biomechanical properties were evaluated. Differences were assessed by one-way ANOVA with post hoc Bonferroni-corrected comparisons (P < 0.05). Tnmd-/-/Chm1-/- IVDs displayed increased DHI and histomorphological scores that indicated increased IVD degeneration compared to the WT and Tnmd-/- groups. Double knockout IVDs required significantly less torque and energy to initiate torsional failure. Creep parameters were comparable between all groups, except for the slow time constant, which indicated faster outward fluid flow. Tnmd-/- IVDs lost fluid faster than the WT group, and this effect was amplified in the double knockout IVDs. Knocking out Tnmd and Chm1 affects IVD fluid flow and organ-level biomechanical function and therefore may play a role in contributing to IVD degeneration. Larger effects of the Tnmd and Chm1 double knockout mice compared to the Tnmd single mutant suggest that Chm1 may play a compensatory role in the Tnmd single mutant IVDs.

Citation

Theodor Di Pauli von Treuheim, Olivia M Torre, Emily D Ferreri, Philip Nasser, Angelica Abbondandolo, Manuel Delgado Caceres, Dasheng Lin, Denitsa Docheva, James C Iatridis. Tenomodulin and Chondromodulin-1 Are Both Required to Maintain Biomechanical Function and Prevent Intervertebral Disc Degeneration. Cartilage. 2021 Dec;13(2_suppl):604S-614S