Osteoarthritic Mice Exhibit Enhanced Prostaglandin E₂ and Unchanged Calcitonin Gene-Related Peptide Release in a Novel Isolated Knee Joint Model

BEATE AVERBECK, KARL RUDOLPHI, and MARTIN MICHAELIS

ABSTRACT.

Objective. Osteoarthritis (OA) is a painful degenerative joint disease. To assess joint nociceptor activation indirectly, we used a novel in vitro knee joint preparation and determined the release of calcitonin gene-related peptide (CGRP) and prostaglandin E₂ (PGE₂) in osteoarthritic mice.

Methods. We studied STR/1N mice, which spontaneously develop OA, along with CD-1 mice as controls and C57/Bl6 mice with unilateral collagenase-induced OA and C57/Bl6 control mice. The release of CGRP and PGE₂ from tibial and femoral joint preparations was determined separately in vitro with enzyme immunoassays; we investigated both basal release and release induced by stimulation with capsaicin (CAP, 1 µM) or bradykinin (BK, 10 µM).

Results. Basal PGE₂ release from femoral and tibial preparations increased by 79% and 97%, respectively, in STR/1N mice between 6 and 18 weeks of age when they developed OA, while age-matched CD-1 mice exhibited only a weak increase (23%). BK-evoked PGE₂ release was significantly higher in 18-week-old STR/1N mice (931 ± 98 pg/ml and 759 ± 82 pg/ml from femoral and tibial preparations, respectively) than in age-matched CD-1 controls (236 ± 38 pg/ml and 246 ± 34 pg/ml). CAP stimulation induced a significant CGRP release, which, however, did not correlate with the temporal development of OA in STR/1N mice. Tibial but not femoral joint preparations from mice with collagenase-induced OA exhibited a significantly enhanced release upon BK stimulation compared to sham controls, while CAP-induced CGRP release did not reveal such difference.

Conclusion. Basal and evoked PGE₂ release from knee joint preparations rose while osteoarthritic alterations developed, whereas CGRP release remained unaltered. The increased PGE₂ release may contribute to enhanced nociceptor sensitivity underlying chronic OA pain. (J Rheumatol 2004; 31:2013-20)

Key Indexing Terms:

OSTEOARTHRITIS
PAIN
CALCITONIN GENE-RELATED PEPTIDE RELEASE
PROSTAGLANDIN E₂ RELEASE
MOUSE KNEE JOINT
MOUSE STRAINS

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From Aventis Pharma Deutschland GmbH, Frankfurt, Germany.

B. Averbeck, PhD; K. Rudolphi, DVM; M. Michaelis, MD, PhD.

Address reprint requests to Dr. rer. nat B. Averbeck, Aventis Pharma Deutschland GmbH, DG Thrombosis and Degenerative Joint Diseases, Industriepark Höchst, Building H821, 65926 Frankfurt, Germany. E-mail: beate.averbeck@aventis.com

Submitted October 28, 2003; revision accepted April 27, 2004.

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