Trial reportThe Journal of biological chemistry2012
Detrimental role for human high temperature requirement serine protease A1 (HTRA1) in the pathogenesis of intervertebral disc (IVD) degeneration.
Trial report in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
42 citing papers in PubMed.
- Giant cell tumor of bone: exploring HtrA1 as a potential predictor of recurrence.Archives of orthopaedic and trauma surgery · 2026Article
- Human papillomavirus E7 inhibits immune responses in keratinocytes by activating HTRA1‑mediated mitophagy.International journal of molecular medicine · 2026Article
- Drug retention after intradiscal administration.Drug delivery · 2024Article
- Identification of highly potent and selective HTRA1 inhibitors.Bioorganic & medicinal chemistry letters · 2024Article
- Identification of HTRA1, DPT and MXRA5 as potential biomarkers associated with osteoarthritis progression and immune infiltration.BMC musculoskeletal disorders · 2024Article
- Immunization against nucleus pulposus antigens to accelerate degenerative disc disease in a rabbit model.Frontiers in veterinary science · 2024Article
- Protocol for Biospecimen Collection and Analysis Within the BACPAC Research Program.Pain medicine (Malden, Mass.) · 2023Article
- HTRA1 from OVX rat osteoclasts causes detrimental effects on endplate chondrocytes through NF-κB.Heliyon · 2023Article
- Transcriptomic analyses of joint tissues during osteoarthritis development in a rat model reveal dysregulated mechanotransduction and extracellular matrix pathways.Osteoarthritis and cartilage · 2023Article
- Targeting Autophagy for Developing New Therapeutic Strategy in Intervertebral Disc Degeneration.Antioxidants (Basel, Switzerland) · 2022Review
- Current Perspectives on Nucleus Pulposus Fibrosis in Disc Degeneration and Repair.International journal of molecular sciences · 2022Review
- The Proteolysis of ECM in Intervertebral Disc Degeneration.International journal of molecular sciences · 2022Review
- Elevated inflammatory gene expression in intervertebral disc tissues in mice with ADAM8 inactivated.Scientific reports · 2021Article
- Adrenoceptor Expression during Intervertebral Disc Degeneration.International journal of molecular sciences · 2020Article
- Expression and activity of hyaluronidases HYAL-1, HYAL-2 and HYAL-3 in the human intervertebral disc.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2020Article
- Molecular structure and the role of high-temperature requirement protein 1 in skeletal disorders and cancers.Cell proliferation · 2020Review
- Fibronectin Fragments and Inflammation During Canine Intervertebral Disc Disease.Frontiers in veterinary science · 2020Article
- Galectins-1 and -3 in Human Intervertebral Disc Degeneration: Non-Uniform Distribution Profiles and Activation of Disease Markers Involving NF-κB by Galectin-1.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2019Article
- VEGF vascularization pathway in human intervertebral disc does not change during the disc degeneration process.BMC research notes · 2018Article
- HtrA1 up-regulates expression of MMPs via Erk1/2/Rock-dependent pathways.International journal of clinical and experimental pathology · 2018Article
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 rs11200638 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-1β 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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