Unraveling Binding Interactions between Human RANKL and Its Decoy Receptor Osteoprotegerin

Munasinghe, Aravinda; Lin, Ping; Colina, Coray M.

doi:10.1021/acs.jpcb.7b06687

Cited by 15 publications

(13 citation statements)

References 36 publications

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“…Besides binding RANK, OPG is able to interact with TRAIL and induces apoptosis of tumor cells through the cell-surface receptors death receptor 4 (DR4) and DR5 in the TNFRSF family [9]. The binding mode to RANKL was determined from computational docking and molecular dynamics simulations [10,11]. OPG is expressed in vivo by ECs, VSMCs, and osteoblasts.…”

Section: The Opg/rankl/rank/trail System: Structures Localizationmentioning

confidence: 99%

The Role of Osteoprotegerin and Its Ligands in Vascular Function

Rochette

Méloux

Rigal

et al. 2019

IJMS

117

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The superfamily of tumor necrosis factor (TNF) receptors includes osteoprotegerin (OPG) and its ligands, which are receptor activators of nuclear factor kappa-B ligand (RANKL) and TNF-related apoptosis-inducing ligand (TRAIL). The OPG/RANKL/RANK system plays an active role in pathological angiogenesis and inflammation as well as cell survival. It has been demonstrated that there is crosstalk between endothelial cells and osteoblasts during osteogenesis, thus establishing a connection between angiogenesis and osteogenesis. This OPG/RANKL/RANK/TRAIL system acts on specific cell surface receptors, which are then able to transmit their signals to other intracellular components and modify gene expression. Cytokine production and activation of their receptors induce mechanisms to recruit monocytes and neutrophils as well as endothelial cells. Data support the role of an increased OPG/RANKL ratio as a possible marker of progression of endothelial dysfunction in metabolic disorders in relationship with inflammatory marker levels. We review the role of the OPG/RANKL/RANK triad in vascular function as well as molecular mechanisms related to the etiology of vascular diseases. The potential therapeutic strategies may be very promising in the future.

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Section: The Opg/rankl/rank/trail System: Structures Localizationmentioning

confidence: 99%

The Role of Osteoprotegerin and Its Ligands in Vascular Function

Rochette

Méloux

Rigal

et al. 2019

IJMS

117

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“…Os processos de osteoclastogênese e de diferenciação de osteoclastos envolvendo RANKL se iniciam com a ligação deste ao seu receptor RANK, o qual é presente na superfície de pré-osteoclastos. Enquanto isso, a OPG, solúvel no plasma, apresenta efeito antirreabsortivo, uma vez que tem alta afinidade por RANKL e impede a interação de RANK (KAPASA et al, 2017;MUNASINGHE;LIN;COLINA, 2017;CHEN et al, 2018;UDAGAWA et al, 2020).…”

Section: Osseointegração De Implantes Dentáriosunclassified

Efeito do uso de fármacos anti-inflamatórios não esteroidais (AINES) na osseointegração de implantes dentários: revisão de literatura / Effect of the use of non-steroid anti-inflammatory drugs (NSAIDs) in the osseointegration of dental implants: literature review

Duarte¹,

Roque²,

Bernardino³

et al. 2022

Braz. J. Hea. Rev.

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A osseointegração de implantes endósseos (OI) é um processo dinâmico, envolvendo diversos tipos celulares, buscando o íntimo contato entre osso alveolar e superfície do implante. Os anti-inflamatórios não esteroidais (AINES) são frequentemente prescritos no pós-operatório da instalação de implantes devido a seu efeito analgésico, entretanto, por interferirem com a atuação de prostaglandinas (PGs) ao inibir enzimas ciclooxigenases (COX), podem prejudicar o processo de OI. Assim, o presente artigo objetivou, mediante uma revisão na literatura científica, analisar a influência do uso de AINES no processo de OI. Para isso, realizou-se uma busca por artigos científicos na base de dados PubMed com os termos "dental implants" AND "osseointegration" AND "antiinflammatory agents, non-steroidal". A busca resultou em 20 manuscritos e, após a leitura de seus resumos, foram selecionados, sem qualquer restrição de ano, 10 artigos. Estes foram lidos na íntegra e corresponderam a pesquisas científicas pré-clínicas e clínicas diretamente relacionadas ao efeito de AINES na OI ou a atuação de COX neste processo. Foram excluídos artigos referentes a outros fármacos e outras revisões de literatura. A maioria dos estudos selecionados sugeriu que os AINES podem intervir negativamente na OI, especialmente se tratando da atividade inibitória proeminentemente sobre COX-2, interferindo no equilíbrio osteoblástico e osteoclástico característico da remodelação óssea contínua. No reparo ósseo, a ativação de COX-2 mostra-se importante na ativação primária de osteoclastos, sendo crucial para turn over ósseo e efetividade de OI. Nota-se, entretanto, escassez de estudos na literatura científica que possibilitem a afirmação concreta da influência de AINES sobre OI.

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“…RANKL and OPG system: One of the main regulators of osteoclast differentiation and function is the RANKL/RANK/OPG system [20,22]. It has been suggested that circulating levels of OPG and RANKL could reflect local bone marrow production [72,73]. The activator of the nuclear factor kappa-B ligand is OPG.…”

Section: New Bone Markersmentioning

confidence: 99%

Bone markers

Konukoğlu¹

2019

Int J Med Biochem

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B one tissue is one of the hardest tissues in the body. It has 3 important functions: mechanical, protective, and metabolic. The mechanical functions of the skeletal muscles are to provide body movement based on attachment to the bones. Contraction allows body movement. The protective function of the bones is the armor provided to internal organs, such as those in the cranium and thorax. Finally, there is the process of hematopoiesis in the bone marrow. The metabolic function of bone provides for the storage of ions, such as calcium, phosphorus, sodium, and magnesium, and the maintenance of hemostasis of these minerals [1][2][3]. This paper is a discussion of new and novel bone markers and preanalytical factors that affect analytical methods. Bone tissue structureBone is a mineralized connective tissue composed of an organic and inorganic structure. The inorganic structure, or mineral structure, of bone is primarily hydroxyapatite Ca10 (PO4) 6 (OH) 2 crystals, as well as magnesium, carbonate, and fluoride. The majority of calcium in the body is in the bones (about 99%). Hydroxyapatite crystals provide resistance to bone [4,5]. The collagen fibrils are the element that provides strength, while hydroxyapatite crystals contribute hardness. The organic matrix forms about half of the dry weight of the bone. Collagen is the major protein of the organic matrix; non-collagen molecular (glycosaminoglycans and glycoproteins, etc.) constitute about 10% of the organic matrix. Although 80% to 90% of collagen is type 1 collagen, other collagen types (type 3, 5, 11, 13 collagen) also make up the matrix structure [2,6,7]. Non-collagen proteins, such as proteoglycans (chondroitin sulfate and proteoglycan), glycoproteins (alkaline phosphatase and osteonectin), glycoproteins containing arginine-glycine-asparagine, (osteopontin and bone sialoprotein), osteoprotogerin, and carboxylated (Gla) proteins (osteocalcin and matrix Gla protein), are also present [8,9].Objectives: Bone has a dynamic metabolism that includes modeling and remodeling activities. There is continuous communication between 3 types of bone cells; osteoblasts, osteoclasts, and osteocytes. Local stress factors, cytokines, and hormones play an important role in these relationships. The most important structural component of bone is type 1 collagen. During the formation and degradation of collagen, some compounds are secreted into the bloodstream, and in cases of diseases involving the bone, the quantity of these compounds increases both in blood concentration and urinary excretion. Some bone markers are secreted into the circulation during bone formation, and some are released into the circulation through bone resolution. Bone markers reflect changes in bone metabolism due to primary or secondary causes, rather than a specific bone disease. Some factors affecting the results should be considered during the evaluation of changes. These factors include preanalytical effects, such as age, gender, diurnal rhythm, and analytical problems. This review is a summary of the cur...

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Unraveling Binding Interactions between Human RANKL and Its Decoy Receptor Osteoprotegerin

Cited by 15 publications

References 36 publications

The Role of Osteoprotegerin and Its Ligands in Vascular Function

The Role of Osteoprotegerin and Its Ligands in Vascular Function

Efeito do uso de fármacos anti-inflamatórios não esteroidais (AINES) na osseointegração de implantes dentários: revisão de literatura / Effect of the use of non-steroid anti-inflammatory drugs (NSAIDs) in the osseointegration of dental implants: literature review

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