Systematic analysis of lncRNAs, miRNAs and mRNAs for the identification of biomarkers for osteoporosis in the mandible of ovariectomized mice

Osteoporosis is a complex and multifactorial disease caused by an imbalance between bone formation and resorption. Post-menopausal women with endogenous estrogen deficiency suffer from systemic bone loss and osteoporosis, and are at high risk of this affecting the jaw bones. MicroRNAs (miRNAs or miRs) have been implicated in the mechanisms of metabolic bone diseases and are expressed at differential levels in alveolar bone following ovariectomy. In the present study, we systematically analyzed the expression profiles of miRNAs, mRNAs and long non-coding RNA (lncRNAs) in the mandible of ovariectomized (OVX) mice. A complex miRNA-mRNA-lncRNA regulatory network was constructed based on differentially expressed RNAs. Two core differentially expressed genes (DEGs), namely, LRP2 binding protein (Lrp2bp) and perilipin 4 (Plin4), significantly influenced the network targeted by differentially expressed miRNAs. Moreover, peroxisome proliferator-activated receptor (PPAR) and insulin signaling pathways were significantly dysregulated in the mandible of OVX mice. Several differentially expressed lncRNAs were also implicated in the two signaling pathways, which influenced mandible development by forming competing endogenous RNA. On the whole, our data indicate that the comprehensive analysis of miRNAs, mRNAs and lncRNAs provides insight into the pathogenesis of estrogen deficiency-induced osteoporosis in the mandible. This study proposes potential biomarkers for diagnosis or therapeutic targets for osteoporosis which may aid in the development of novel drugs for the treatment of osteoporosis.