Network and pathway-based analyses of genes associated with osteoporosis

Abstract

Osteoporosis (OP) is a disease characterized by bone mass loss, bone microstructure damage, increased bone fragility, and easy fracture. The molecular mechanism underlying OP remains unclear. In this study, we identified 217 genes associated with OP, and formed a gene set [OP-related genes gene set (OPgset)]. The highly enriched GOs and pathways showed OPgset genes were significantly involved in multiple biological processes (skeletal system development, ossification, and osteoblast differentiation), and several OP-related pathways (Wnt signaling pathway, osteoclast differentiation, steroid hormone biosynthesis, and adipocytokine signaling pathway). Besides, pathway crosstalk analysis indicated three major modules, with first module consisted of pathways mainly involved in bone development-related signaling pathways, second module in Wnt-related signaling pathway and third module in metabolic pathways. Further, we calculated degree centrality of a node and selected ten key genes/proteins, including TGFB1, IL6, WNT3A, TNF, PTH, TP53, WNT1, IGF1, IL10, and SERPINE1. We analyze the K-core and construct three k-core sub-networks of OPgset genes. In summary, we for the first time explored the molecular mechanism underlying OP via network- and pathway-based methods, results from our study will improve our understanding of the pathogenesis of OP. In addition, these methods performed in this study can be used to explore pathogenesis and genes related to a specific disease.

Identification and Functional Annotation of Genes Related to Bone Stability in Laying Hens Using Random Forests

“…Furthermore, the mitogen-activated protein kinase (MAPK) signalling pathway was enriched, which is also very important for skeletal development and, in particular, for chondrogenesis [ 92 ]. These observations are in accordance with recent results from pathway analyses [ 25 , 93 ].…”

miR-134-5p inhibits osteoclastogenesis through a novel miR-134-5p/Itgb1/MAPK pathway

“…Rab27a interference rescued dysfunctional osteoblasts originating from OVX mice and was restrained by miR-124 to attenuate osteoclastogenesis (42,43). Moreover, previous studies have shown that Hyal1 expression is upregulated via osteoclast formation and that Serpine1 is enriched in osteoporosis patients (44,45). In addition, Antxr1 is also involved in RANKL-induced osteoclastogenesis (46).…”

Helicobacter pylori Related Diseases and Osteoporotic Fractures (Narrative Review)

“…Among adults, a small male predominance of HPI-related outcomes has been found in a meta-analysis based on 169 studies (OR 1.12, 95% CI: 1.09, 1.15) [ 407 ]. Shared genetic basis underlying OP and a variety of HPI-related chronic extra-gastroduodenal diseases (CAD, DM, dyslipidemia) has been reported [ 408 , 409 , 410 , 411 , 412 , 413 , 414 , 415 , 416 , 417 , 418 , 419 ]. The shared biology and bi-(multi-)directional links between OP and HPI-associated chronic diseases apply particularly to CVD, CKD, CLD, DM and neurodegenerative diseases; these disorders are interrelated and often accompanied by OP/OF [ 420 , 421 , 422 , 423 , 424 , 425 , 426 , 427 , 428 , 429 , 430 ], and the risk of OP/OF increases when two or more HPI-associated chronic diseases are present.…”