The long noncoding RNA Crnde regulates osteoblast proliferation through the Wnt/β-catenin signaling pathway in mice.

Abstract

In the past decade, a growing importance has been placed on understanding the significance of long noncoding RNAs (lncRNAs) in regulating development, metabolism, and homeostasis. Osteoblast proliferation and differentiation are essential elements in skeletal development, bone metabolism, and homeostasis. However, the underlying mechanisms of lncRNAs in the process of osteoblast proliferation and differentiation remain largely unknown. Through comprehensive analysis of lncRNAs during bone formation, we show that colorectal neoplasia differentially expressed (Crnde), previously viewed as a cancer-related lncRNA, is an important regulator of osteoblast proliferation and differentiation. Crnde was found to be expressed in osteoblasts, and its expression was induced by parathyroid hormone. Furthermore, Crnde knockout mice developed a low bone mass phenotype due to impaired osteoblast proliferation and differentiation. Overexpression of Crnde in osteoblasts promoted their proliferation, and conversely, reduced Crnde expression inhibited osteoblast proliferation. Although ablation of Crnde inhibited osteoblast differentiation, overexpression of Crnde restored it. Finally, we provided evidence that Crnde modulates bone formation through Wnt/β-catenin signaling. Therefore, our data suggest that Crnde is a novel regulator of bone metabolism.