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Glutamatergic signalling in the osteoarthritic knee

Mason, Deborah Jane, Brakspear, Karen Sarah, Wilson, C., Williams, R. and Kotwal, Rahul S. 2010. Glutamatergic signalling in the osteoarthritic knee. International Journal of Experimental Pathology 91 (2) , A34-A35. 10.1111/j.1365-2613.2009.00690.x

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Abstract

Introduction Pain is the major burden in osteoarthritis. Synovial fluid concentrations of the neurotransmitter glutamate are increased in arthritis (1, 2), and contribute to nociception, inflammation and degradation via receptors in nerves and musculoskeletal tissues (3). We investigated whether glutamate signalling components are expressed in human osteoarthritic knees. Materials and Methods Subchondral bone was removed after total knee arthroplasty (n = 2, TKR, Kellgren Lawrence grade 3) or from tibial drill hole sites after high tibial osteotomy (n = 2, HTO, KL grades 2 and 3) for osteoarthritis. Meniscus samples, obtained after TKR (n = 3), were sub-divided according to anatomical site (anterior horn, body or posterior horn; inner vascular or outer avascular). RNA was extracted, reverse transcribed and RT-PCR performed for GAPDH, the glutamate transporter EAAT-1, and glutamate receptors (NR2A, GluR3 and KA1). Quantitative RT-PCR assessed differences in the expression of EAAT-1, a dominant negative splice variant called EAAT-1ex9skip, type I collagen and osteocalcin.Results EAAT-1, NR2A and KA1 mRNAs were expressed in subchondral bone, alongside high osteocalcin expression, indicating RNA derived from osteoblasts and osteocytes. EAAT-1 expression was significantly reduced in the anterior vs. the middle or posterior zones (ANOVA, P < 0.001) in one patient. RT-PCR indicated differential expression of EAAT-1 between medial and lateral bone, however these differences were not significant by quantitative RT-PCR. EAAT-1ex9skip mRNA appeared less abundant in HTO than TKR patients. Type 1 collagen, EAAT-1, EAAT-1ex9skip, NR2A, AMPA GluR3 and KA1 were expressed in human meniscus. EAAT-1 expression normalised to GAPDH did not vary with anatomical site in the meniscus but EAAT-1ex9skip was significantly more common within the outer zones (ANOVA, P = 0.040) and in the posterior horns (ANOVA, P = 0.038). Discussion We have shown for the first time that glutamate transporters and receptors are abundant in the meniscus and subchondral bone of patients with osteoarthritis and that EAAT-1 and EAAT-1ex9skip expression may vary with anatomical location and pathology. Activation of these receptors and transporters by the increased synovial fluid concentrations of glutamate that occur in osteoarthritis may contribute to pathological changes and nociception

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > QR Microbiology
Publisher: Wiley-Blackwell
ISSN: 0959-9673
Last Modified: 18 Sep 2017 10:20
URI: http://orca.cf.ac.uk/id/eprint/69047

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