Background: MicroRNAs control cell signaling during osteoblast differentiation. Results: miR-218, which is highly expressed in osteoblasts and cancer cells metastatic to bone, targets three inhibitors of Wnt signaling, Sclerostin, Dickkopf2, and secreted frizzled-related protein2. Conclusion: miR-218 promotes differentiation of normal osteoblast and the osteomimetic bone-homing properties of tumor cells. Significance: miR-218 may be a universal stimulator of Wnt-signaling during bone development and cancer progression.

Nonsyndromic cleft lip with or without a cleft palate (NSCL/P) is among the most common human congenital birth defects and imposes a substantial physical and financial burden on affected individuals. Here, we conduct a case-control-based GWAS followed by two rounds of replication; we include six independent cohorts from China to elucidate the genetic architecture of NSCL/P in Chinese populations. Using this combined analysis, we identify a new locus at 16p13.3 associated with NSCL/P: rs8049367 between CREBBP and ADCY9 (odds ratio ¼ 0.74, P ¼ 8.98 Â 10 À 12 ). We confirm that the reported loci at 1q32.2, 10q25.3, 17p13.1 and 20q12 are also involved in NSCL/P development in Chinese populations. Our results provide additional evidence that the rs2235371-related haplotype at 1q32.2 could play a more important role than the previously identified causal variant rs642961 in Chinese populations. These findings provide information on the genetic basis and mechanisms of NSCL/P.

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