Treuheim, Theodor Di Paulivon and Torre, Olivia M. and Ferreri, Emily D. and Nasser, Philip and Abbondandolo, Angelica and Caceres, Manuel Delgado and Lin, Dasheng and Docheva, Denitsa and Iatridis, James C. (2021) Tenomodulin and Chondromodulin-1 Are Both Required to Maintain Biomechanical Function and Prevent Intervertebral Disc Degeneration. CARTILAGE, 13 (2_SUPP): 1947603521. 604S-614S. ISSN 1947-6035, 1947-6043
Full text not available from this repository. (Request a copy)Abstract
Objective 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. Design 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). Results 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. Conclusion 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LOW-BACK-PAIN; ANULUS FIBROSUS; INJURY; INSTABILITY; DISEASE; SYSTEM; SPINE; intervertebral disc; biomechanics; tenomodulin; chondromodulin-1; structure function relationship |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Unfallchirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Sep 2022 08:42 |
| Last Modified: | 16 Sep 2022 08:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47533 |
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