Figure 5.

Altered collagen dynamics in osteogenesis imperfecta murine (oim/oim) forelimbs

(A) During WT forelimb development (E11.5-E14.5) and growth (P3, P35), collagen content significantly increased, and (B) the ratios of collagen isoforms associated with type I fibrillogenesis were dependent on age (p < 0.0001; one-way ANOVA). Values shown are average of n=3 replicates and scale bars represent the standard deviation (Table S2).

(C) LC-MS/MS analysis of CS and IN fractions of oim/oim and wild-type forelimbs validated a decrease in COL1A2 abundance (Table S5; two-tailed t-test; ∗∗∗∗p < 0.0001).

(D) The ratios of collagen chains associated with type I collagen fibrillogenesis in oim/oim and wild-type forelimbs. Although the ratios between α1(I):α2(I) and α1(I):α2(V) were significantly different in oim/oim forelimbs (p < 0.05, two-tailed t-test), the other ratios were not affected by the mutation.

(E) In the mutant forelimbs, less COL1A2 was found in the IN fraction, relative to the CS fraction (two-tailed t-test; ∗∗p < 0.01), indicating increased solubility of this collagen chain in oim/oim forelimb, compared to the wild-type.

(F) In contrast, significantly more COL1A1 was found in the IN fraction, relative to the CS fraction, compared to controls (two-tailed t-test; ∗∗p < 0.01).

(G) Increased pyrrolidine cross-links (PYD), relative to the hydroxyproline content (Hyp), was observed in mutant TA tendons from 10-weeks-old mice (n=3; two-tailed t-test; ∗∗∗p < 0.001).