Craniometaphyseal Dysplasia Mutations in ANKH Negatively Affect Human Induced Pluripotent Stem Cell Differentiation into Osteoclasts.

ABSTRACT: We identified osteoclast defects in craniometaphyseal dysplasia (CMD) using an easy-to-use protocol for differentiating osteoclasts from human induced pluripotent stem cells (hiPSCs). CMD is a rare genetic bone disorder, characterized by life-long progressive thickening of craniofacial bones and abnormal shape of long bones. hiPSCs from CMD patients with an in-frame deletion of Phe377 or Ser375 in ANKH are more refractory to in vitro osteoclast differentiation than control hiPSCs. To exclude differentiation effects due to genetic variability, we generated isogenic hiPSCs, which have identical genetic background except for the ANKH mutation. Isogenic hiPSCs with ANKH mutations formed fewer osteoclasts, resorbed less bone, expressed lower levels of osteoclast marker genes, and showed decreas

SUBMITTER: Chen IP 

PROVIDER: S-EPMC5830990 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature