EXPRESSION OF GLUTAMATE RECEPTORS AND TRANSPORTERS IN HUMAN MENISCUS: CORRELATION WITH ANATOMICAL LOCATION, PAIN OR PATHOLOGY

Abstract

Purpose of the study: Since glutamate can activate both nociceptive and pathological processes, we have investigated glutamate signalling in patients with painful and asymptomatic meniscal tears to determine which components are expressed, whether this varies in different anatomical regions of the meniscus and whether it is influenced by pain or degeneration.

Methods and results: Meniscus samples were obtained from two patients undergoing arthroscopic partial meniscal resection for chronic degenerate painful meniscal tears, from one patient with a torn painless meniscus and from the less affected compartment of the knee joint of three patients undergoing total knee arthroplasty. Menisci were dissected into anatomical regions (anterior horn, body, posterior horn, inner vascular, outer avascular), cryosectioned and RNA extracted. RNA was reverse transcribed and PCR performed for the housekeeping gene GAPDH and glutamate receptor subunits (NR2A, AMPA GluR3, KA1). Absolute quantitative RT-PCR assessed mRNA expression of glutamate transporters (EAAT-1, EAAT-1ex9skip) and type I collagen after normalisation to GAPDH or total RNA.

Human meniscus expressed GAPDH, type 1 collagen, EAAT-1, EAAT-1ex9skip, NR2A, AMPA GluR3 and KA1 mRNAs. Levels of EAAT-1 expression, normalised to GAPDH, did not differ between the inner and outer halves, or in the anterior, middle or posterior regions of menisci from the less affected compartments of arthritic knees. EAAT-1 expression appeared greater in the 2 painful, compared with the single non-painful meniscus. Interestingly, EAAT-1ex9skip was significantly more common within the outer zones (ANOVA, P=0.040) and in the posterior horns of the menisci (ANOVA, p=0.038).

Conclusion: We have shown for the first time that glutamate receptors and transporters are expressed in human meniscus providing a potential mechanism underlying the pathophysiology of pain associated with a torn meniscus. Our preliminary data indicate that EAAT-1 and EAAT-1ex9skip expression may vary with extent of damage and anatomical location in the human meniscus.