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. 2019 Feb 7;4(3):e124701. doi: 10.1172/jci.insight.124701

Figure 9. Impaired synthesis of extracellular matrix (ECM) components and disrupted chondrogenic differentiation of TRIP11-mutant cells.

Figure 9

(A) Number of chondrogenic nodules at day 7 of transdifferentiation of fibroblasts (fibroblast-induced chondrocytes, FDC) in controls and patients. (B) Size of the chondrogenic nodules at day 7, as exemplified for case 6 by inverse microscopy of live cells in (C). Scale bar: 100 μm. (D) Alcian blue staining of transdifferentiated patient-derived primary and matched control FDC cultures at days 1–7 of chondrogenic differentiation demonstrates reduced matrix production in patient cells. Scale bars: 150 μm. (E) Quantification of total glycosaminoglycan/proteoglycan content in FDCs; data points represent the mean of triplicate values (n = 3); error bars indicate ± SD. (F and G) Quantitative ELISA shows that secreted markers of terminal differentiation, COL10A1 and pro-MMP13, are significantly reduced in supernatants of patient-derived cultures at late time points of the transdifferentiation protocol. CTL, controls 1 and 2; ODCD, odontochondrodysplasia cases 3, 6, and 10; ACG1A, achondrogenesis 1A cases A1 and A2. Data points represent the mean of quadruplicate values (n = 4); error bars indicate ± SD. (H) Quantitative ELISA of pro-collagen, type 1, α-1 (pro-COL1A1) in conditioned FDC supernatants. Data represent mean ± SD of quadruplicates (2-way ANOVA with Bonferroni’s post hoc test); *P ≤ 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.