Cyclooxygenase-2 deficiency causes delayed ossification of lumbar vertebral endplates.
Am J Transl Res. 2018;10(three):718-730
Authors: Ding Q, Ren Y, Che H, Ma C, Li H, Yu S, Zhang Y, An H, O’Keefe RJ, Chen D, Block JA, Yin G, Li T
Primarily based on earlier findings that cyclooxygenase-2 (COX-2) is a vital molecule in chondrocyte differentiation and skeletal restore, we hypothesized that COX-2 deficiency or inhibition impacts the ossification of vertebral endplates (VEP) and degeneration of intervertebral discs (IVD) and thus is concerned within the pathogenesis of low again ache (LBP). We aimed to delineate the COX-2 working mechanism and its interacting molecules, and to discover the impact of NSAIDs and selective COX-2 inhibitor on degenerative spinal ailments. Right here, lumbar spinal samples harvested from Cox-2 mutant (Cox-2-/-) and wild kind (WT) mice had been used for histological examinations. Nucleus pulposus (NP) cells remoted from rat had been handled with PGE-2. Mouse endplate chondrocytes (mEC) remoted from mice had been handled with a recombinant sonic hedgehog (Shh) protein. A mouse IVD organ tradition system was established and handled COX-2 inhibitor Celecoxib. Human lumbar endplate chondrocytes had been cultured and handled with Celecoxib. Immunohistochemical (IHC) research had been achieved within the human and mouse VEP samples. Radiographic and histological examinations revealed delayed VEP ossification in Cox-2-/- mice in comparison with WT ones. Decreased PGE-2 expression was discovered to advertise Shh expression in rat NP cells, whereas Shh elevated noggin expression in mEC. IHC confirmed that noggin expression was elevated whereas pSmad1 expression decreased within the VEP of Cox-2-/- mice. Human VEP samples from sufferers with extreme IVD degeneration confirmed decreased expression of Shh and noggin and elevated expression of COX-2 and pSmad1 in contrast with milder instances. In cultured mouse IVDs and human endplate chondrocytes, Celecoxib enhanced expression of Shh and noggin and decreased Smad1 phosphorylation. In conclusion, COX-2/PGE-2 axis performs an vital function in VEP ossification and IVD degeneration by crosstalk with Shh and BMP signaling pathways. These findings might facilitate medical use of COX-2 inhibitor to forestall LBP development.
PMID: 29636862 [PubMed]