Lin, Dasheng and Alberton, Paolo and Caceres, Manuel Delgado and Prein, Carina and Clausen-Schaumann, Hauke and Dong, Jian and Aszodi, Attila and Shukunami, Chisa and Iatridis, James C. and Docheva, Denitsa (2020) Loss of tenomodulin expression is a risk factor for age-related intervertebral disc degeneration. AGING CELL, 19 (3): e13091. ISSN 1474-9718, 1474-9726
Full text not available from this repository. (Request a copy)Abstract
The intervertebral disc (IVD) degeneration is thought to be closely related to ingrowth of new blood vessels. However, the impact of anti-angiogenic factors in the maintenance of IVD avascularity remains unknown. Tenomodulin (Tnmd) is a tendon/ligament-specific marker and anti-angiogenic factor with abundant expression in the IVD. It is still unclear whether Tnmd contributes to the maintenance of IVD homeostasis, acting to inhibit vascular ingrowth into this normally avascular tissue. Herein, we investigated whether IVD degeneration could be induced spontaneously by the absence of Tnmd. Our results showed that Tnmd was expressed in an age-dependent manner primarily in the outer annulus fibrous (OAF) and it was downregulated at 6 months of age corresponding to the early IVD degeneration stage in mice. Tnmd knockout (Tnmd(-)(/)(-)) mice exhibited more rapid progression of age-related IVD degeneration. These signs include smaller collagen fibril diameter, markedly lower compressive stiffness, reduced multiple IVD- and tendon/ligament-related gene expression, induced angiogenesis, and macrophage infiltration in OAF, as well as more hypertrophic-like chondrocytes in the nucleus pulposus. In addition, Tnmd and chondromodulin I (Chm1, the only homologous gene to Tnmd) double knockout (Tnmd(-)(/)(-)Chm1(-)(/)(-)) mice displayed not only accelerated IVD degeneration, but also ectopic bone formation of IVD. Lastly, the absence of Tnmd in OAF-derived cells promoted p65 and matrix metalloproteinases upregulation, and increased migratory capacity of human umbilical vein endothelial cells. In sum, our data provide clear evidences that Tnmd acts as an angiogenic inhibitor in the IVD homeostasis and protects against age-related IVD degeneration. Targeting Tnmd may represent a novel therapeutic strategy for attenuating age-related IVD degeneration.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHONDROMODULIN-I; EXTRACELLULAR-MATRIX; ANNULUS FIBROSUS; NUCLEUS PULPOSUS; SELF-RENEWAL; CELL; ANGIOGENESIS; OSTEOARTHRITIS; LOCALIZATION; REGENERATION; angiogenesis; annulus fibrous; intervertebral disc degeneration; knockout mice; nucleus pulposus; tenomodulin |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Unfallchirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Mar 2021 07:14 |
| Last Modified: | 30 Mar 2021 07:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45080 |
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