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Intervertebral disc (IVD) disorder is often caused by the defect of annulus fibrosus (AF), especially that of the outer AF. Studies about the mechanisms governing the development of the outer AF are needed for a better understanding of pathogenesis of IVD defects. Glycosaminoglycans (GAGs) are essential components of extracellular matrix (ECM) in AF. FAM20B is a newly identified xylose kinase that catalyzes the biosynthesis of GAGs. In this study, we created Fam20B conditional knockout (cKO) mice in which FAM20B was inactivated in type I collagen-expressing cells, the main type of cells in the outer AF of IVD. The cKO mice showed severe spine deformity and remarkable IVD defects associated with AF malformation. The AF of cKO mice had a lower level of chondroitin sulfate and heparan sulfate, and the outer AF cells lost their normal fibroblast-like morphology and acquired chondrocyte phenotypes, expressing a higher level of Sox 9 and type II collagen along with a reduced level of type I collagen. The level of phospho-Smad 2 and phospho-Smad 3, and that of scleraxis, a downstream target molecule of canonical TGF-β signaling pathway were significantly lower in the AF of cKO mice. The AF in cKO mice also manifested altered levels in the molecules associated with the activations of MAPK pathway; the changes included the increase of phospho-P38 and phospho-ERK and a decrease of phospho-JNK. These results indicate that FAM20B plays an essential role in the development of AF by regulating the TGF-β signaling and MAPK signaling pathways.
This article was published in the following journal.
Name: Biochimica et biophysica acta. Molecular basis of disease
Intervertebral disc (IVD) herniations are currently treated with interventions that leave the IVD with persistent lesions prone to further herniations. Annulus fibrosus (AF) repair has become of inter...
Focal defects in the annulus fibrosus (AF) of the intervertebral disc (IVD) arising from herniation have detrimental impacts on the IVD's mechanical function. Thus, biomimetic-based repair strategies ...
Postoperative magnetic resonance imaging (MRI) after microdiscectomy for lumbar disc herniation frequently shows spinal canal compression by the remaining annulus, which gradually decreases over time....
Annulus fibrosus (AF) impairment is associated with reherniation, discogenic pain, and disc degeneration after surgical partial discectomy. Due to a limited intrinsic healing capacity, defects in the ...
Erratum: "The Mechanical Role of the Radial Fibers Network Within the Annulus Fibrosus of the Lumbar Intervertebral Disc: A Finite Elements Study" ASME J. Biomech. Eng., 2018, 141(2), p. 021006: DOI: 10.1115/1.4041769.
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Outer portion of the intervertebral disc that surrounds the NUCLEUS PULPOSUS.
An INTERVERTEBRAL DISC in which the NUCLEUS PULPOSUS has protruded through surrounding ANNULUS FIBROSUS. This occurs most frequently in the lower lumbar region.
A type of heart valve surgery that involves the repair, replacement, or reconstruction of the annulus of the MITRAL VALVE. It includes shortening the circumference of the annulus to improve valve closing capacity and reinforcing the annulus as a step in more complex valve repairs.
A type of heart valve surgery that involves the repair, replacement, or reconstruction of the annuli of HEART VALVES. It includes shortening the circumference of the annulus to improve valve closing capacity and reinforcing the annulus as a step in more complex valve repairs.
Inactivation of viruses by non-immune related techniques. They include extremes of pH, HEAT treatment, ultraviolet radiation, IONIZING RADIATION; DESICCATION; ANTISEPTICS; DISINFECTANTS; organic solvents, and DETERGENTS.