Association of Gremlin-2 gene polymorphisms with osteoporosis risk in Chinese postmenopausal women

Abstract

The Gremlin-2 (GREM2) plays crucial roles in modulating bone homeostasis through the bone morphogenetic protein-2 pathway. However, GREM2 gene variants in osteoporosis were less frequent in a Chinese population. Therefore, the present study recruited 310 patients with osteoporosis and 339 healthy postmenopausal women to assess the correlation of GREM2 gene polymorphisms with the risk of osteoporosis. Polymerase chain reaction (PCR) and Sanger sequencing were utilized to genotype samples. The results showed that GREM2 gene rs4454537, not rs11588607, polymorphism was significantly associated with an increased risk of osteoporosis in postmenopausal women. Moreover, stratified analyses indicated a significant association between rs4454537 polymorphisms and body mass index of <25 kg/m2. Additionally, the association between GREM2 rs4454537 polymorphism and clinical characteristics was assessed, which showed that this locus decreased the bone mineral density (BMD) in postmenopausal osteoporotic individuals. Furthermore, individuals with CC genotype appeared to have a higher GREM2 expression compared with those bearing the TT genotype of rs4454537 polymorphism. However, the genotype distribution of rs4454537 polymorphism showed no statistical difference between osteoporotic patients as a function of fracture status. In summary, GREM2 rs4454537 polymorphism decreases BMD and increases osteoporotic risk in postmenopausal women.

Effect of Rhizoma Drynariae on differential gene expression in ovariectomized rats with osteoporosis based on transcriptome sequencing

“…Gremlin-2, a key bone morphogenetic protein (GREM2) (BMP) antagonist, can competitively bind BMP receptors to regulate the activity of BMP ligands, thus it plays a crucial role in regulating bone homeostasis ( 45 ). In the Yu Feng’s study ( 46 ) showed that the GREM2 gene polymorphisms were positively associated with the risk of osteoporosis in postmenopausal women. It has been shown that GREM2 negatively regulates osteoblast differentiation by participating in the regulation of the Wnt/catenin signaling pathway ( 47 ).…”

Recent Advance in Regulatory Effect of GRP120 on Bone Metabolism

“…(1) activates the Ras/ERK1/2 pathway; inhibits p38 phosphorylation, and promotes osteogenic differentiation (2) regulates the integrin family to promote osteogenic differentiation (3) significantly inhibits adipogenesis (4) regulates the integrin family to inhibit osteogenesis and promote adipogenicity (5) promotes the phosphorylation level of p38, inhibits the phosphorylation of ERK1/2, inhibits osteogenesis, and promotes adipogenic differentiation [36] Dex, 10μM Significantly inhibits the apoptotic effect of Dex and improves the survival rate of BMMSCs [14] MC3T3-E1 precursor osteoblasts…”

“…According to reports, more than 200 million people in China have osteoporosis, and the average prevalence of this condition among the elderly is about 15.7%; osteoporosis in women is as high as 80%, especially in postmenopausal women [4,5]. Osteoarthritis is another common bone metabolism disease; its incidence in adults is more than 10%.…”

“…Low bone mass and bone tissue microarchitecture degeneration are the main pathological features of osteoporosis which to increased bone fragility and fracture susceptibility and even death. According to reports, more than 200 million people in China have osteoporosis, and the average prevalence of this condition among the elderly is about 15.7%; osteoporosis in women is as high as 80%, especially in postmenopausal women [ 4 , 5 ]. Osteoarthritis is another common bone metabolism disease; its incidence in adults is more than 10%.…”

Genetic variation in NOD1/CARD4 and NOD2/CARD15 immune sensors and risk of osteoporosis

“…Genetic factors affect bone turnover and can result in the reduction in mass to ∼50-80% [4,6,7]. Gene polymorphisms may contribute to osteoporosis and impact bone mineral density (BMD) [7][8][9][10][11][12]. However, recently clinical and molecular study results emphasize that inflammation process also can effects on bone turnover in the osteoporosis [13][14][15].…”