Defective WNT signaling may protect from articular cartilage deterioration – a quantitative MRI study on subjects with a heterozygous WNT1 mutation

WNT signaling is of key importance in chondrogenesis and defective WNT signaling may contribute to the pathogenesis of osteoarthritis and other cartilage diseases. Biochemical composition of articular cartilage in patients with aberrant WNT signaling has not been studied. Our objective was to assess the knee articular cartilage in WNT1 mutation-positive individuals using a 3.0T MRI unit to measure cartilage thickness, relaxation times, and texture features. Cohort comprised mutation-positive (N = 13; age 17–76 years) and mutation-negative (N = 13; 16–77 years) subjects from two Finnish families with autosomal dominant WNT1 osteoporosis due to a heterozygous missense mutation c.652T>G (p.C218G) in WNT1. All subjects were imaged with a 3.0T MRI unit and assessed for cartilage thickness, T2 and T1ρ relaxation times, and T2 texture features contrast, dissimilarity and homogeneity of T2 relaxation time maps in six regions of interest (ROIs) in the tibiofemoral cartilage. All three texture features showed opposing trends with age between the groups in the medial tibiofemoral cartilage (P = 0.020–0.085 for the difference of the regression coefficients), the mutation-positive individuals showing signs of cartilage preservation. No significant differences were observed in the lateral tibiofemoral cartilage. Cartilage thickness and means of T2 relaxation time did not differ between groups. Means of T1ρ relaxation time were significantly different in one ROI but the regression analysis displayed no differences. Our results show less age-related cartilage deterioration in the WNT1 mutation-positive than the mutation-negative subjects. This suggests, that the WNT1 mutation may alter cartilage turnover and even have a potential cartilage-preserving effect.