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Role of HTRA1 in Intervertebral Disc Degeneration


, : Role of HTRA1 in Intervertebral Disc Degeneration.

Human HTRA1 is a highly conserved secreted serine protease that degrades numerous extracellular matrix proteins. We have previously identified HTRA1 as being up-regulated in osteoarthritic patients and as having the potential to regulate matrix metalloproteinase (MMP) expression in synovial fibroblasts through the generation of fibronectin fragments. In the present report, we have extended these studies and investigated the role of HTRA1 in the pathogenesis of intervertebral disc (IVD) degeneration. HTRA1 mRNA expression was significantly elevated in degenerated disc tissue and was associated with increased protein levels. However, these increases did not correlate with the appearance of rs112638 single nucleotide polymorphism in the promoter region of the HTRA1 gene, as has previously been suggested. Recombinant HTRA1 induced MMP production in IVD cell cultures through a mechanism critically dependent on MEK but independent of IL-1? signaling. The use of a catalytically inactive mutant confirmed these effects to be primarily due to HTRA1 serine protease activity. HTRA1-induced fibronectin proteolysis resulted in the generation of various sized fragments, which when added to IVD cells in culture, caused a significant increase in MMP expression. Furthermore, one of these fragments was identified as being the amino-terminal fibrin- and heparin-binding domain and was also found to be increased within HTRA1-treated IVD cell cultures as well as in disc tissue from patients with IVD degeneration. Our results therefore support a scenario in which HTRA1 promotes IVD degeneration through the proteolytic cleavage of fibronectin and subsequent activation of resident disc cells.

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Other references

Doss, M., 1979: Therapy and prevention of acute hepatic phophyrias. Deutsche Medizinische Wochenschrift 104(43): 1509-1511

Larsen, TB., 1982: Mass population build-up of Anaphaeis aurota F. in Oman (Lepidoptera, Pieridae). Atalanta (Marktleuthen): 131: 42-47

Demidov, B.S.; Dorozhkova, I.R.; Kartanbaev, A.K., 1968: On the question of the bacteriological diagnosis and surgical treatment of pulmonary aspergillosis. Cases of 3 patients (a 25-yr-old woman and 36- and 34-yr-old men) who developed pulmonary aspergillosis at first misdiagnosed as tuberculosis are reported and the diagnosis and treatment of aspergillosis are discussed.

Ohguchi Y.; Kuroda Y., 1987: Effects of omega conotoxin in isolated rat superior cervical ganglia. Journal of the Physiological Society of Japan 49(8-9): 380

Mateo-Cid, L.-Elena; Pedroche, F., F., 2004: The occurrence of Neogoniolithon fosliei (Heydrich) Setchell et Mason in the Mexican Caribbean and the relationship of this species to N. solubile (Foslie et Howe) Setchell et Mason (Corallinales, Rhodophyta). We report Neogoniolithon foshei from the Mexican Caribbean, after comparing its type from the Red Sea and lectotype from Puerto Rico with specimens of N. solubile from Mexico. We propose that these two taxa are conspecific, since they display a si...

Anonymous, 2017: Schedule of Events. Innovations 12(2s Suppl 2): S20-S27

Eastman, C.R., 1908: Dates Of Early Santorin And Ischian Eruptions. Science 27(700): 855-855

Hazard, J.; Mérot, J.; Klotz, A.; Potel, M., 1969: Ascites revealing thyroid deficiency. Annales de Medecine Interne 120(11): 755-759

Saager P.M.; Sweerts J P.; Ellermeijer H.J., 1990: A simple pore water sampler for coarse sandy sediments of low porosity. A simple, inexpensive, and highly efficient centrifuge tube allows nearly complete extraction of interstitial water from coarse, sandy sediments with porosities as low as 32%. The method is fast (5 min), efficient (55-92% of the available water is...

Pellet, J.; Tafforeau, L.; Lucas-Hourani, M.; Navratil, V.; Meyniel, L.; Achaz, G.; Guironnet-Paquet, A.; Aublin-Gex, A.; Caignard, G.; Cassonnet, P.; Chaboud, A.; Chantier, T.; Deloire, A.; Demeret, C.; L.B.eton, M.; Neveu, G.; Jacotot, L.; Vaglio, P.; Delmotte, S.; Gautier, C.; Combet, C.; Deleage, G.; Favre, M.; Tangy, F.; Jacob, Y.; Andre, P.; Lotteau, V.; Rabourdin-Combe, C.; Vidalain, P.O., 2010: ViralORFeome: an integrated database to generate a versatile collection of viral ORFs. Large collections of protein-encoding open reading frames (ORFs) established in a versatile recombination-based cloning system have been instrumental to study protein functions in high-throughput assays. Such 'ORFeome' resources have bee...