Mm. Hyttinen et al., Inactivation of one allele of the type II collagen gene alters the collagen network in murine articular cartilage and makes cartilage softer, ANN RHEUM D, 60(3), 2001, pp. 262-268
Objective-To evaluate the influence of inactivation of one allele ("heteroz
ygous knockout" or "heterozygous inactivation") of the type II procollagen
gene (Col2a1) on the biomechanical properties and structure of the articula
r cartilage and subchondral bone in 15 month old mice.
Methods-Indentation stiffness of the humerus head articular cartilage was m
easured by a microindentation method. Cartilage and subchondral bone were p
repared for digital densitometry of proteoglycans (PGs), polarised light mi
croscopy (PLM) of collagen, and osteoarthrosis (OA) grading.
Results-Heterozygous inactivation of the Col2a1 gene softened articular car
tilage (p=0.002) as measured by indentation stiffness ((mean (SEM) 0.50 (0.
07) MPa v 0.94 (0.13) MPa in controls). Fibrillar collagen network exhibite
d lower birefringence in the intermediate (p=0.04) and deep zones (p=0.01)
of cartilage by PLM, indicating either decreased collagen content or a lowe
r degree of fibril parallelism in the knockout mice. The total and zonal th
icknesses of articular cartilage were unchanged. Zonal PG contents did not
differ significantly. In knockout mice, the prevalence of superficial fibri
llation-that is, a sign of OA, was higher than in controls (73% v 21%, p=0.
002). The collagen induced birefringence of the superficial zone was not re
duced. The subchondral bone volume fraction was lower in knockout mice than
in controls, 31% v 43% (p=0.01), and optical retardation values in PLM of
bone collagen were slightly but significantly lower (p=0.01).
Conclusion-Heterozygous inactivation of the Col2a1 gene made articular cart
ilage softer, altered the collagenous network, reduced subchondral bone vol
ume, and altered its microstructure. Changes in the cartilage collagen netw
ork probably contributed to increased susceptibility to OA.