A BMP4 in the spent media of the NCM460 cells was markedly reduced following ARSB knockdown (p<0.001; one-way ANOVA with Tukey-Kramer post-test; n=6).
B. BMP4 was significantly reduced in the serum of the ARSB-null mice (p<0.01, unpaired t-test, two-tailed; n=5).
C. Following ARSB silencing, the membrane-bound BMP4 increased significantly (p<0.001, one-way ANOVA with Tukey-Kramer post-test; n=3). Treatment with chondroitinase ABC reduced the membrane-bound BMP4 (p<0.001, one-way ANOVA with Tukey-Kramer post-test; n=3). In contrast, there was no effect of keratanase treatment.
D. Representative Western blot demonstrates increase in the intestinal membrane-associated Bmp-4 of male and female ARSB-null mice, compared to gender and age-matched C57BL/6J controls.
E. The quantity of BMP4 that co-immunoprecipitated with C4S in the NCM460 cells increased significantly when ARSB was silenced by siRNA (p<0.0001, unpaired t-test, two-tailed; n=3 independent experiments).
F. Following treatment with chondroitinase ABC, the BMP4 in the spent media increased significantly when ARSB was silenced (p<0.001), although the cellular BMP4 and total BMP4 were reduced (p<0.001, p<0.01, respectively; one way ANOVA with Tukey-Kramer post-test; n=3).
G. mRNA expression of CHST 11 was unaffected by treatment with chondroitinase ABC (n=6). [ARSB=arylsulfatase B; BMP=bone morphogenetic protein; ChABC=chondroitinase ABC; F=female; CHST11=carbohydrate (chondroitin 4) sulfotransferase 11; Kase=keratanase; M=male; N.D.=no difference]