Lumbar disc degeneration is linked to a carbohydrate sulfotransferase 3 variant.

Lumbar disc degeneration (LDD) is associated with both genetic and environmental factors and affects many people worldwide. A hallmark of LDD is loss of proteoglycan and water content in the nucleus pulposus of intervertebral discs. While some genetic determinants have been reported, the etiology of LDD is largely unknown.

Structure and biology of the intervertebral disk in health and disease.

The intervertebral disks along the spine provide motion and protection against mechanical loading. The 3 structural components, nucleus pulposus, annulus fibrosus, and cartilage endplate, function as a synergistic unit, though each has its own role. The cells within each of these components have distinct origins in development and morphology, producing specific extracellular matrix proteins that are organized into unique architectures fit for intervertebral disk function.

Post-transcriptional regulation of CLMP mRNA is controlled by tristetraprolin in response to TNFalpha via c-Jun N-terminal kinase signalling.

During spermatogenesis, extensive restructuring of blood-testis barrier takes place to facilitate the migration of preleptotene/leptotene spermatocytes from the basal to the adluminal compartment in the seminiferous epithelium. However, the biochemical mechanisms involved in this event remain elusive. Recent studies have shown that pro-inflammatory cytokine TNFalpha (tumour necrosis factor alpha) plays a crucial role in this event by inhibiting the expression of tight junction proteins in Sertoli cells.

Expression of CLMP, a novel tight junction protein, is mediated via the interaction of GATA with the Kruppel family proteins, KLF4 and Sp1, in mouse TM4 Sertoli cells.

Regulation of tight junction protein expressions in Sertoli cells is important for germ cell translocation across the blood-testis-barrier (BTB) during spermatogenesis. In this study, a novel tight junction transmembrane protein, CLMP, found expressed in mouse testis was shown to localize at the BTB along with the tight junction marker ZO-1. By the use of transient transfection assay performed in a mouse Sertoli cell-cell line, TM4 cells, we showed that the minimal CLMP promoter was located between nucleotides -550 and -288 relative to the translation start site.

Nectin-2 expression in testicular cells is controlled via the functional cooperation between transcription factors of the Sp1, CREB, and AP-1 families.

Nectin-2, a major protein component of the adherens junctions (AJs), is found between Sertoli cells and germ cells in the seminiferous epithelium. Recent studies have shown that the expression of nectin-2 gene in testis is crucial to maintain normal spermatogenesis since male knockout mice lacking nectin-2 gene are sterile and possess morphologically abnormal spermatozoa. However, the molecular mechanisms governing its basal transcription remain poorly understood.