Anti-osteoporosis activity of red yeast rice extract on ovariectomy-induced bone loss in rats.

Osteoporosis is the most common bone disease, affecting millions of people worldwide and leading to significant morbidity and high costs. Monacolin K, an extract of red yeast rice (RYR, Hongqu), plays important roles in the management of dyslipidemia, coronary heart disease, and diabetes. Our study aimed to investigate the protective effect of monacolin K on ovariectomy-induced bone loss in rats. Fifty female Sprague-Dawley rats were randomly divided into a sham-operated and five ovariectomized (OVX) groups: OVX with vehicle, OVX with fluvastatin, and OVX with RYR extract of three graded doses. Bone mineral density (BMD), biochemical markers, and cell viability were analyzed by dual energy X-ray absorptiometry, enzyme-linked immunosorbent assay, and 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays. Gene expression was evaluated by real-time polymerase chain reaction amplification and western blot. Our results showed that administration of RYR extract markedly increased the bone mineral density in OVX rats. Moreover, RYR extract decreased the levels of bone turnover markers, including osteocalcin and tartrate resistant acid phosphatase activity. The MMT assay revealed that RYR extract treatment significantly improved the osteoblast viabilities in a dose-dependent manner (P < 0.05). At the molecular level, we further demonstrated that RYR extract enhanced the expression of Bmp2 and Bmp4 both at the mRNA and protein levels. Collectively, these data suggested RYR extract could protect against osteoporosis in ovariectomized rats, most likely through activation of BMP2/4 expression.

Whole exome sequencing implicates PTCH1 and COL17A1 genes in ossification of the posterior longitudinal ligament of the cervical spine in Chinese patients.

Ossification of the posterior longitudinal ligament (OPLL) of the cervical spine is a complex multifactorial disease. Patients with OPLL commonly present with symptoms in their 40s or 50s. The genetic basis of OPLL remains poorly understood. Exome capture combined with massively parallel DNA sequencing has been proposed as an efficient strategy to search for disease-causing genes of both monogenic and multigenic disorders. To identify candidate pathogenic genes associated with OPLL, we performed whole exome sequencing (WES) on two unrelated southern Chinese OPLL patients. The entire DNA coding region of the candidate genes was amplified by PCR and Sanger sequenced. The common single nucleotide polymorphisms were analyzed by association studies. WES revealed p.T265S/PTCH1, p.P1232L/PTCH1, and p.T902S/COL17A1 mutants in the two female cases with mixed OPLL. These were confirmed by Sanger sequencing. p.P1232L/PTCH1, p.N1374D/COL17A1 and p.T902S/COL17A1 were subsequently identified in three males with continuous OPLL and one female with mixed OPLL. The association studies indicated that the SNPs rs805698 and rs4918079 in COL17A1 were significantly associated with OPLL. This study suggests that WES may be a practical approach to revealing significant genetic involvement in OPLL. Variants of the PTCH1 and COL17A1 genes may contribute to the development of OPLL.