Tricho-dento-osseous (TDO) syndrome is a rare autosomal dominant disease resulting from distal-less homeobox 3 (DLX3) mutation.1,2 Accumulative bone density in alveolar bone is a clinically favorable phenotype for TDO patients. However, the limited number of bone marrow mesenchymal stem cells (BMSCs) in TDO patients restricts their application. Since TDO-specific induced pluripotent stem cells (iPSCs) can yield a large variety of patient cells as the important cell source to investigate specific tissue/organ development, establish disease models, and develop new treatment approaches, we established TDO-iPS cells with mutant DLX3 (c.533A > G, Q178R) of the host cells. Our previous research indicated that mutant DLX3 could down-regulate H19 to regulate bone formation.3 In this study, we successfully generated and verified TDO-iPSCs, and compared the osteogenic differentiation capacity from TDO-iPSCs to mesenchymal stem cells (MSCs) and from normal human iPSCs to iPS-MSCs. We also predicted that H19 could sponge miR-29c-3p and lysine demethylase 5B (KDM5B) was the target gene of miR-29c-3p. We found transfected miR-29c-3p inhibitor down-regulated miR-29c-3p and up-regulated the expression of KDM5B and osteogenic biomarker. Previous research suggested that KDM5B promoted osteo-differentiation by binding to the promoter region of alkaline phosphatase (ALP), RUNX family transcription factor 2 (RUNX2), and osteocalcin (OCN).4 We deduced that H19, miR-29c-3p, and KDM5B, together serving as a ceRNA (competing endogenous RNA) network, were regulated by DLX3 to affect osteo-differentiation, which is a novel pathway to regulate bone formation and shed light on the treatment of bone-related diseases.