Absence of collagen IX accelerates hypertrophic differentiation in the embryonic mouse spine through a disturbance of the Ihh-PTHrP feedback loop

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• 作者：Matthias Kamper ; Mats Paulsson ; Frank Zaucke
• 关键词：Cartilage ; Extracellular matrix ; Collagen ; Intervertebral disc ; Spine
• 刊名：Cell and Tissue Research
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：367
• 期：2
• 页码：359-367
• 全文大小：
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Human Genetics; Proteomics; Molecular Medicine;
• 出版者：Springer Berlin Heidelberg
• ISSN：1432-0878
• 卷排序：367

文摘

Collagen IX (Col IX) is a component of the cartilage extracellular matrix and contributes to its structural integrity. Polymorphisms in the genes encoding the Col IX ɑ2- and ɑ3-chains are associated with early onset of disc degeneration. Col IX-deficient mice already display changes in the spine at the newborn stage and premature disc degeneration starting at 6 months of age. To determine the role of Col IX in early spine development and to identify molecular mechanisms underlying disc degeneration, the embryonic development of the spine was analyzed in Col IX −/− mice. Histological staining was used to show tissue morphology at different time points. Localization of extracellular matrix proteins as well as components of signaling pathways were analyzed by immunohistochemistry. Developing vertebral bodies of Col IX −/− mice were smaller and already appeared more compact at E12.5. At E15.5, vertebral bodies of Col IX −/− mice revealed an increased number of hypertrophic chondrocytes as well as enhanced staining for the terminal differentiation markers alkaline phosphatase and collagen X. This correlates with an imbalance in the Ihh-PTHrP signaling pathway at this time point, reflected by an increase of Ihh and a concomitant decrease of PTHrP expression. An accelerated hypertrophic differentiation caused by a disturbed Ihh-PTHrP signaling pathway may lead to a higher bone mineral density in the vertebral bodies of newborn Col IX −/− mice and, as a result, to the early onset of disc degeneration.