Systematic analysis of long non-coding RNA and mRNA profiling using RNA sequencing in the femur and muscle of ovariectomized rats.

OBJECTIVE: To investigate the expression profile of lncRNAs in bone and skeletal muscle of ovariectomized (OVX) rats. METHODS: Six-month-old female Sprague-Dawley (SD) rats were divided into OVX group (ovariectomized, n=12) and sham group (sham-operated, n=12). After 12 weeks, RNA-seq was used to analyze the differential expression of lncRNAs and mRNAs in femur and quadriceps between two groups. Dys-regulated expression of lncRNAs was confirmed by qRT-PCR. The cis and trans-regulatory functions were analyzed to determine their function and biological processes. Lastly, GO and KEGG analyses were performed to assess the biological relevance of genes in each profile. RESULTS: A total of 17 lncRNAs and 440 mRNAs were differentially expressed in the femur. Thirteen lncRNAs and 292 mRNAs were differentially expressed in the quadriceps. qRT-PCR results were in consistent with the RNA-seq data. Among them, ENSRNOT00000090777 was found in both femur and quadriceps samples. Bioinformatics analysis found that LNC_004549 participated in the differentiation of skeletal and skeletal muscle. CONCLUSIONS: The expression profile of lncRNAs was significantly altered in femur and quadriceps of OVX rat models, which may offer new insights into pathogenesis of osteoporosis and sarcopenia and potentially provide novel therapeutic targets.

Gushukang inhibits osteocyte apoptosis and enhances BMP-2/Smads signaling pathway in ovariectomized rats.

BACKGROUND: Traditional herbal formula Gushukang (GSK) has been clinically applied to treat primary osteoporosis, which can stimulate osteoblastogenesis and improve calcium homeostasis. However, it remains unknown the mechanism that GSK against ovariectomized (OVX) induced damage. PURPOSE: The aim of this study was to investigate the effect of GSK on BMP-2/Smsds signaling pathway and osteocyte apoptosis which has been reported to play a central role in bone remodeling. STUDY DESIGN: OVX in rat was established and GSK was administered. RESULTS: BMP-2/Smsds signaling pathway was inhibited and the number of apoptotic osteocytes was increased in OVX rats. Treatment with GSK significantly enhanced BMP-2/Smsds signaling pathway by up-regulating the expression of BMP-2, p-Smad1 and p-Smad5, Osterix and Runx2, and inhibited osteocyte apoptosis by up-regulating Bcl-xl and down-regulating Bak, which were consistent with histological changes revealed by ALP, Trap and TUNEL staining. GSK treatment improved bone mass and micro-structure of trabecular bone at distal femur in OVX rats shown by BMD, micro-CT measurement and HE staining. CONCLUSION: These data suggest that GSK exhibited protective effects on promoting bone formation and precluding osteocyte apoptosis. The underlying mechanism may be attributed to its regulation on BMP-2/Smads signaling pathway and Bcl2 family.