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sRANKL (total) Human ELISA (Osteoprotegerin Ligand)

  • Regulatory status:RUO
  • Type:Sandwich ELISA, Biotin-labelled antibody
  • Other names:Receptor Activator for Nuclear Factor κ B Ligand, osteoprotegerin ligand, TNF-related activation-induced cytokine
  • Species:Human
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Cat. No. Size Price


RD193004200R 96 wells (1 kit)
PubMed Product Details
Technical Data

Type

Sandwich ELISA, Biotin-labelled antibody

Applications

Serum, Plasma-EDTA, Plasma-Heparin, Plasma-Citrate

Sample Requirements

5 µl/well

Shipping

At ambient temperature. Upon receipt, store the product at the temperature recommended below.

Storage/Expiration

Store the kit at 2–8°C. Under these conditions, the kit is stable until the expiration date (see label on the box).

Calibration Curve

Calibration Range

0.5–32 pmol/l

Limit of Detection

0.4 pmol/l

Intra-assay (Within-Run)

n = 8; CV = 9.4%

Inter-assay (Run-to-Run)

n = 4; CV = 12.0%

Spiking Recovery

96,30%

Dilutation Linearity

112,30%

Crossreactivity

  • bovine Non-detectable
  • cat Non-detectable
  • dog Non-detectable
  • goat Non-detectable
  • hamster Non-detectable
  • horse Non-detectable
  • monkey Non-detectable
  • mouse Non-detectable
  • rabbit Non-detectable
  • rat Non-detectable
  • sheep Non-detectable
  • chicken Not tested
  • human Yes
  • pig Yes (recommended dilution 1:12)
Summary

Features

  • It is intended for research use only
  • The total assay time is about 20 hours
  • The kit measures total sRANKL in serum and plasma (EDTA, citrate, heparin)
  • Assay format is 96 wells
  • Quality Controls are native protein based
  • Standard is serum protein based
  • Components of the kit are provided ready to use, concentrated or lyophilized

Research topic

Bone and cartilage metabolism, Oncology

Summary

sRANKL, receptor activator of nuclear factor (NF)-κB ligand (also: osteoprotegerin ligand, OPGL), is a part of the TNF superfamily with high similarity to other members of that protein species. (SwissProt Nr. O14788).

Three isoforms are produced by alternate splicing, two type II membrane proteins (ISOFORM 1, 317 AA, and ISOFORM 3, 270 AA), and a secreted molecule (ISOFORM 2, 244 AA). ISOFORM 1 is identical to previously reported RANKL and possesses intracellular, transmembrane, and extracellular domains; ISOFORM 2 does not have the intracellular and transmembrane domains, and ISOFORM 3 does not have the intracellular domain. A soluble form arises by proteolytic processing from membrane isoforms.

Although all forms are bioactive, the membrane-bound proteins seem to be the homeostatic forms, while the production of soluble RANKL signals pathological conditions.

RANKL, RANK, and osteoprotegerin (OPG) have been identified as the key molecular regulation system for bone remodelling. RANKL is the main stimulatory factor for the formation of mature osteoclasts and is essential for their survival. Therefore, an increase in RANKL expression leads to bone resorption and bone loss. RANKL is produced by osteoblastic lineage cells and activated T lymphocytes. It activates its specific receptor RANK, which is located on osteoclasts and dendritic cells. The effects of RANKL are counteracted by OPG, which is secreted by various tissues and acts as an endogenous soluble receptor antagonist.

Imbalances of the RANKL/OPG system have been related to the pathogenesis of Paget’s disease, benign and malignant bone tumors, postmenopausal osteoporosis, rheumatoid arthritis, bone metastases and hypercalcemia. Several studies using animal models have shown that restoring the RANKL/OPG balance (e.g. by administering OPG) reduces the severity of these disorders.

Indication

  • Postmenopausal and senile osteoporosis
  • Diseases with locally increased bone resorption activity
  • Paget´s disease
  • Periodontal disease
  • Cardiovascular disease, arterial calcification
  • Inflammatory diseases
  • Immunological disorders
  • Arthritis
  • Oncology
References to Product

References

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  • Barbagallo I, Vanella A, Peterson SJ, Kim DH, Tibullo D, Giallongo C, Vanella L, Parrinello N, Palumbo GA, Di Raimondo F, Abraham NG, Asprinio D. Overexpression of heme oxygenase-1 increases human osteoblast stem cell differentiation. J Bone Miner Metab. 2010 May;28 (3):276-88
  • Boyapati A, Msihid J, Fiore S, van Adelsberg J, Graham NM, Hamilton JD. Sarilumab plus methotrexate suppresses circulating biomarkers of bone resorption and synovial damage in patients with rheumatoid arthritis and inadequate response to methotrexate: a biomarker study of MOBILITY. Arthritis Res Ther. 2016 Oct 6;18 (1):225
  • Buondonno I, Rovera G, Sassi F, Rigoni MM, Lomater C, Parisi S, Pellerito R, Isaia GC, D'Amelio P. Vitamin D and immunomodulation in early rheumatoid arthritis: A randomized double-blind placebo-controlled study. PLoS One. 2017 Jun 5;12(6):e0178463. doi: 10.1371/journal.pone.0178463
  • Cao H, Wu Y, Li Q, Wu Y, Zhou Q, Røe OD, Chen Y, Wang R, Wang D. Serum sRANKL/OPG predict recurrence after radiofrequency catheter ablation of lone atrial fibrillation. Int J Cardiol. 7 September 2013;
  • Cao H, Zhou Q, Wu Y, Li Q, Roe OD, Chen Y, Wu Z, Wang D. Preoperative Serum Soluble Receptor Activator of Nuclear Factor-kappaB Ligand and Osteoprotegerin Predict Postoperative Atrial Fibrillation in Patients Undergoing Cardiac Valve Surgery. Ann Thorac Surg. 2013 Sep;96 (3):800-6
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  • Chen CH, Chen HA, Liao HT, Liu CH, Tsai CY, Chou CT. Soluble receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin in ankylosing spondylitis: OPG is associated with poor physical mobility and reflects systemic inflammation. Clin Rheumatol. 2010 Oct;29 (10):1155-61
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  • Davenport C, Harper E, Rochfort KD, Forde H, Smith D, Cummins PM. RANKL Inhibits the Production of Osteoprotegerin from Smooth Muscle Cells under Basal Conditions and following Exposure to Cyclic Strain. J Vasc Res. 2018;55(2):111-123.
  • Foo JP, Polyzos SA, Anastasilakis AD, Chou S, Mantzoros CS. The effect of leptin replacement on parathyroid hormone, RANKL-osteoprotegerin axis, and Wnt inhibitors in young women with hypothalamic amenorrhea. J Clin Endocrinol Metab. 2014 Nov;99 (11):E2252-8
  • Ford ML, Smith ER, Tomlinson LA, Chatterjee PK, Rajkumar C, Holt SG. FGF-23 and osteoprotegerin are independently associated with myocardial damage in chronic kidney disease stages 3 and 4. Another link between chronic kidney disease-mineral bone disorder and the heart. Nephrol Dial Transplant. 2011 Jul 12;
  • Friedmann A, Ozmeric N, Bernimoulin JP, et al. Receptor activator of NF-kappaB ligand (RANKL) and CD 31 expressions in chronic periodontitis patients before and after surgery. Cent Eur J Immunol. 2014;39(4):508-17.
  • Friedrich MJ, Wimmer MD, Schmolders J, Strauss AC, Ploeger MM, Kohlhof H, Wirtz DC, Gravius S, Randau TM. RANK-ligand and osteoprotegerin as biomarkers in the differentiation between periprosthetic joint infection and aseptic prosthesis loosening. World J Orthop. 2017 Apr 18;8(4):342-349. doi: 10.5312/wjo.v8.i4.342
  • Konca Degertekin C, ORCID: http://orcid.org/0000-0003-0299-6596, Turhan Iyidir O, Aktas Yilmaz B, Elbeg S, Pasaoglu OT, Pasaoglu H, Cakir N, Arslan M. RANKL/Osteoprotegerin System and Bone Turnover in Hashimoto Thyroiditis. Calcif Tissue Int. 2016 Jun 22;
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  • Krela-Kazmierczak I, Kaczmarek-Rys M, Szymczak A, Michalak M, Skrzypczak-Zielinska M, Drweska-Matelska N, Marcinkowska M, Eder P, Lykowska-Szuber L, Wysocka E, Linke K, Slomski R. Bone Metabolism and the c.-223C > T Polymorphism in the 5'UTR Region of the Osteoprotegerin Gene in Patients with Inflammatory Bowel Disease. Calcif Tissue Int. 2016 Sep 17;
  • Kuo PL, Liao SH, Hung JY, Huang MS, Hsu YL. MicroRNA-33a functions as a bone metastasis suppressor in lung cancer by targeting parathyroid hormone related protein. Biochim Biophys Acta. 2013 Jun;1830 (6):3756-66
  • Kyrtsonis MC, Vassilakopoulos TP, Siakantaris MP, Kokoris SI, Gribabis DA, Dimopoulou MN, Angelopoulou MK, Pangalis GA. Serum syndecan-1, basic fibroblast growth factor and osteoprotegerin in myeloma patients at diagnosis and during the course of the disease. Eur J Haematol . Apr;72(4):252-8 (2004)
  • Linda Johansson, Lisbeth Ärlestig, Heidi Kokkonen, Mikael Brink, Solbritt Rantapää-Dahlqvist; An increased concentration of receptor activator of nuclear factor kappa-B ligand pre-dates the onset of rheumatoid arthritis, Rheumatology, Volume 56, Issue 12, 1 December 2017, Pages 2190–2196, https://doi.org/10.1093/rheumatology/kex339
  • Lipe B, Kambhampati S, Veldhuizen PV, Yacoub A, Aljitawi O, Mikhael J. Correlation between markers of bone metabolism and vitamin D levels in patients with monoclonal gammopathy of undetermined significance (MGUS). Blood Cancer J. 2017;7(12):646. Published 2017 Dec 14. doi:10.1038/s41408-017-0015-x
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  • Nezami N, Safa J, Eftekhar-Sadat AT, Salari B, Ghorashi S, Sakhaee K, Khosraviani K. Lovastatin raises serum osteoprotegerin level in people with type 2 diabetic nephropathy. Clin Biochem. 2010 Nov;43 (16-17):1294-9
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  • Ren W, Blasier R, Peng X, Shi T, Wooley PH, Markel D. Effect of oral erythromycin therapy in patients with aseptic loosening of joint prostheses. Bone. 2009 Apr;44 (4):671-7
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References to Summary

References to RANKL

  • Hofbauer L.C et al. Effect of oral contraceptives on circulatingosteoprotegerin and soluble RANK ligand serum levels in healthy young women. Clin Endocrinol (2004) 60: 214–219
  • Ito S. et al. Crystal structure of the extracellular domain of mouse ligand at2.2-A resolution. J Biol Chem (2002) 22: 6631–6636.
  • Lam J. et al. Crystal structure of the TRANCE/RANKL cytokine reveals determinants of receptorligand specifity. J Clin Invest (2001) 108: 971–979.
  • Lacey D.L, et al., Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell (1998), 93:165–176.
  • Kong Y.Y. et al., OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature (1999), 397: 315–323.
  • Hsu H. et al., Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc Natl Acad Sci (1999), 96:3540–3545.
  • Josien R. et al, TRANCE, a tumor necrosis factor family member, enhances the longevity and adjuvant properties of dendritic cells in vivo. J Exp Med (2000), 191: 495–502.
  • Fuller K. et al., TRANCE is necessary and sufficient for osteoblast-mediated activation of bone resorption in osteoclasts. J Exp Med (1998), 188: 997–1001.
  • Nakashima T. et. al., Protein expression and functional difference of membrane-bound and soluble receptor activator of NF-kappaB ligand: modulation of the expression by osteotropic factors and cytokines. Biochem Biophys Res Commun (2000), 275(3):768–775.
  • Kong Y.Y. et al., Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature (1999), 402: 304–309.
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  • Hofbauer LC, et al. The role of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin in the pathogenesis and treatment of metabolic bone diseases. J Clin Endocrinol Metab (2000), 85: 2355–2363.
  • Teitelbaum S.L., Bone resorption by osteoclasts. Science (2000), 289: 1504–1508.
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