RANKL biology: bone metabolism, the immune system, and beyond

Ono, Tetsu; Hayashi, Muneaki; Sasaki, Fumio; Nakashima, Tomoki

doi:10.1186/s41232-019-0111-3

Cited by 329 publications

(256 citation statements)

References 113 publications

Supporting

Mentioning

216

Contrasting

Unclassified

Order By: Relevance

“…[2][3][4]. TNFRSF11 is expressed in different organs of the human body, such as liver, bone, muscle, intestinal tract, adrenal gland, and other tissues [5]. TNFRSF11 (RANK) was initially identified and demonstrated to play a role in bone dissolution and lymph node development mainly through the RANK/RANKL/ OPG pathway [6].…”

Section: Introductionmentioning

confidence: 99%

Association of Genetic Polymorphisms in TNFRSF11 with the Progression of Genetic Susceptibility to Gastric Cancer

Fan

Pan

et al. 2020

Journal of Oncology

View full text Add to dashboard Cite

Objective. To investigate the relationship between polymorphism of TNFRSF11 gene rs9533156 and rs2277438 and susceptibility to gastric cancer. Methods. A case-control study was conducted to select 577 cases of primary gastric cancer and 678 cases of normal control. We extracted whole blood genomic DNA and amplified the target gene fragment by PCR. The genotyping and allele were tested through the snapshot method. Results. In this case-control study, we observed that there was a difference in the genotype distribution of TNFRSF11 gene rs9533156 between the case group and the control group. The frequency distribution of TC heterozygous mutation in the case group was higher than that in the control group. The smoking rate in the case group (34.49%) was higher than that in the control group (27.29%), and the difference in frequency distribution between the two groups was statistically significant (P=0.006). Our findings suggest that TNFRSF11 rs9533156 is associated with susceptibility to GC, which is more evident among elderly patients (>62 years), nonsmokers, and patients who do not consume alcohol. The analysis of the relationship between the TNFSF11 gene rs9533156 site variant and clinical factors of gastric cancer showed that, compared with the tumor size <2 cm group, patients with tumor size ≥2 cm and whom carrying rs9533156 site mutations had a higher frequency distribution, and the difference was statistically significant (P=0.022). Compared with the nonhyperglycemic group, the frequency distribution of patients with rs9533156 site mutations in the diabetes group was higher, and the difference was statistically significant (P<0.001). Conclusion. This study shows that there is a correlation between smoking and the occurrence of gastric cancer. Based on our research, the functional SNP TNFRSF11 TC genotype may be an indicator of individual susceptibility to GC. The mutation at rs9533156 may be related to the size of gastric cancer. The mutation rate of rs9533156 of TNFSF11 gene is higher in diabetic gastric cancer patients.

show abstract

Section: Introductionmentioning

confidence: 99%

Association of Genetic Polymorphisms in TNFRSF11 with the Progression of Genetic Susceptibility to Gastric Cancer

Fan

Pan

et al. 2020

Journal of Oncology

View full text Add to dashboard Cite

show abstract

“…Thus, the communication between osteoblasts/osteocytes and osteoclasts, play a crucial role during the bone remodeling process [ 95 ]. The osteoblasts/osteocytes can regulate the osteoclastogenesis by synthetizing RANKL or OPG (decoy receptor sequestering RANKL), which can promote or suppress osteoclastogenesis, respectively [ 96 ]. For example, under mechanical loading, the osteoblasts synthesize OPG via IL-6 stimulation, decreasing osteoclast formation [ 97 ].…”

Section: Osteoblast/osteoclast Balance In Bone Remodeling and Repamentioning

confidence: 99%

Influence of the TGF-β Superfamily on Osteoclasts/Osteoblasts Balance in Physiological and Pathological Bone Conditions

Jann

Gascon

Roux

et al. 2020

IJMS

View full text Add to dashboard Cite

The balance between bone forming cells (osteoblasts/osteocytes) and bone resorbing cells (osteoclasts) plays a crucial role in tissue homeostasis and bone repair. Several hormones, cytokines, and growth factors—in particular the members of the TGF-β superfamily such as the bone morphogenetic proteins—not only regulate the proliferation, differentiation, and functioning of these cells, but also coordinate the communication between them to ensure an appropriate response. Therefore, this review focuses on TGF-β superfamily and its influence on bone formation and repair, through the regulation of osteoclastogenesis, osteogenic differentiation of stem cells, and osteoblasts/osteoclasts balance. After introducing the main types of bone cells, their differentiation and cooperation during bone remodeling and fracture healing processes are discussed. Then, the TGF-β superfamily, its signaling via canonical and non-canonical pathways, as well as its regulation by Wnt/Notch or microRNAs are described and discussed. Its important role in bone homeostasis, repair, or disease is also highlighted. Finally, the clinical therapeutic uses of members of the TGF-β superfamily and their associated complications are debated.

show abstract

“…Consequently, general inflammatory cell infiltration makes a significant contribution to osteoclast formation and bone turnover. 94 , 97 The RANKL:OPG ratio determines the extent of osteoclastogenesis and is subject to a myriad of external influences such as osteotropic agents, inflammation and ageing. 97 – 99 There are a number of clinical interventions to prevent osteoclastic bone loss, from oestrogens to bisphosphonates to denosumab (anti-RANKL monoclonal antibodies).…”

Section: Mechanisms Of Bone Pathophysiology In Spamentioning

confidence: 99%

“… 94 , 97 The RANKL:OPG ratio determines the extent of osteoclastogenesis and is subject to a myriad of external influences such as osteotropic agents, inflammation and ageing. 97 – 99 There are a number of clinical interventions to prevent osteoclastic bone loss, from oestrogens to bisphosphonates to denosumab (anti-RANKL monoclonal antibodies). However, it has been noted that few cells in vertebrae affected by AS express RANKL, 100 suggesting these cells may not augment osteoclast differentiation or function.…”

Section: Mechanisms Of Bone Pathophysiology In Spamentioning

confidence: 99%

Loss and gain of bone in spondyloarthritis: what drives these opposing clinical features?

Clunie

Horwood

2020

Therapeutic Advances in Musculoskeletal

View full text Add to dashboard Cite

The breadth of bone lesion types seen in spondyloarthritis is unprecedented in medicine and includes increased bone turnover, bone loss and fragility, osteitis, osteolysis and erosion, osteosclerosis, osteoproliferation of soft tissues adjacent to bone and spinal skeletal structure weakness. Remarkably, these effects can be present simultaneously in the same patient. The search for a potential unifying cause of effects on the skeleton necessarily focuses on inflammation arising from the dysregulation of immune response to microorganisms, particularly dysregulation of TH17 lymphocytes, and the dysbiosis of established gut and other microbiota. The compelling notion that a common antecedent pathological mechanism affects existing bone and tissues with bone-forming potential (entheses), simultaneously with variable effect in the former but bone-forming in the latter, drives basic research forward and focuses our awareness on the effects on these bone mechanisms of the increasing portfolio of targeted immunotherapies used in the clinic.

show abstract

RANKL biology: bone metabolism, the immune system, and beyond

Cited by 329 publications

References 113 publications

Association of Genetic Polymorphisms in TNFRSF11 with the Progression of Genetic Susceptibility to Gastric Cancer

Association of Genetic Polymorphisms in TNFRSF11 with the Progression of Genetic Susceptibility to Gastric Cancer

Influence of the TGF-β Superfamily on Osteoclasts/Osteoblasts Balance in Physiological and Pathological Bone Conditions

Loss and gain of bone in spondyloarthritis: what drives these opposing clinical features?

Contact Info

Product

Resources

About