Inactivation of one allele of the type II collagen gene alters the collagen network in murine articular cartilage and makes cartilage softer

doi:10.1136/ard.60.3.262

Annals of the Rheumatic Diseases 2001;60:262-268; doi:10.1136/ard.60.3.262

Ann Rheum Dis 2001;60:262-268 ( March )

Extended report

Inactivation of one allele of the type II collagen gene alters the collagen network in murine articular cartilage and makes cartilage softer M M Hyttinen^a, J Töyräs^b, T Lapveteläinen^a, J Lindblom^a, D J Prockop^c, S-W Li^c, M Arita^c, J S Jurvelin^b, H J Helminen^a

^a Department of Anatomy, University of Kuopio, Finland, ^b Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Finland, ^c Centre for Gene Therapy, School of Medicine, MCP Hahnemann University of Health Sciences, Philadelphia, PA, USA

Correspondence to: Dr H J Helminen, Department of Anatomy, University of Kuopio, PO Box 1627, FIN-70211 Kuopio, Finland Heikki.Helminen{at}uku.fi

Accepted for publication 12 July 2000

OBJECTIVE $---$ To evaluate the influence of inactivation of one allele ("heterozygous knockout" or "heterozygous inactivation") of the typeII procollagen gene (Col2a1) on the biomechanical properties andstructure of the articular cartilage and subchondral bone in 15month oldmice.
METHODS $---$ Indentation stiffness of the humerus head articular cartilage was measured by a microindentation method. Cartilage and subchondralbone were prepared for digital densitometry of proteoglycans (PGs),polarised light microscopy (PLM) of collagen, and osteoarthrosis(OA)grading.
RESULTS $---$ Heterozygous inactivation of the Col2a1 gene softened articular cartilage (p=0.002) as measured by indentation stiffness ((mean(SEM) 0.50 (0.07) MPa v 0.94 (0.13) MPa in controls). Fibrillarcollagen network exhibited lower birefringence in the intermediate(p=0.04) and deep zones (p=0.01) of cartilage by PLM, indicatingeither decreased collagen content or a lower degree of fibrilparallelism in the knockout mice. The total and zonal thicknessesof articular cartilage were unchanged. Zonal PG contents did notdiffer significantly. In knockout mice, the prevalence of superficialfibrillation $---$ that is, a sign of OA, was higher than in controls(73% v 21%, p=0.002). The collagen induced birefringence of thesuperficial zone was not reduced. The subchondral bone volumefraction was lower in knockout mice than in controls, 31% v 43%(p=0.01), and optical retardation values in PLM of bone collagenwere slightly but significantly lower (p=0.01).
CONCLUSION $---$ Heterozygous inactivation of the Col2a1 gene made articular cartilage softer, altered the collagenous network, reduced subchondralbone volume, and altered its microstructure. Changes in the cartilagecollagen network probably contributed to increased susceptibilitytoOA.

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