RANKL (TNFSF11), a type II transmembrane protein, is a receptor ligand for NF-κB (RANK). RANKL is an activator of NF-κB. When binding to NF-κB, it induces the differentiation of monocyte/macrophage-lineage cells into osteoclasts and leads to osteoclast precursor maturation. RANKL is critical for osteoclasts maturation, bone modeling, and bone remodeling, as well as the development of lymph nodes (LNs). RANKL/TNFSF11 Protein, Human (HEK293, Fc) is a recombinant human RANKL (G63-D244) with N-terminal mFc tag, which is produced in HEK293 cell.

RANKL (TNFSF11) belongs to TNF family. RANKL is a type II transmembrane protein and is a receptor ligand for NF-κB (RANK). RANKL is an activator of NF-κB. RANKL binds to NF-κB and induces the differentiation of monocyte/macrophage-lineage cells into osteoclasts and leads to osteoclast precursor maturation. In bone tissue, RANKL is expressed by osteoblasts, osteocytes and immune cells, especially in osteoblasts and osteocytes. RANKL is also expressed by T cells and increases proliferation and survival of dendritic cells.
Human RANKL shares 82.02% and 84.44% common aa identity with mouse and rat respectively. Human RANKL consists of cytoplasmic domain (1-47), helical domain (48-68), and extracellular domain (69-317). The soluble chain (140-317) is released when cleaved by enzymes such as matrix metalloproteinases (MMP3 or 7) and ADAM.
RANKL is critical for osteoclasts maturation, bone modeling, and bone remodeling, as well as the development of lymph nodes (LNs).

RANKL (human, -5 ng/mL, 24 h) stimulates migration of a clear cell RCC cell line, Caki-1.
RANKL (human, 24 h) stimulates PAa cell migration and invasion.

RANKL (human, .4 or 2 mg/kg/day, s.c.) induces high bone turnover and decreases bone volume, density, and strength in C57BL/6J female mice.

Immobilized mouse mFc-TNFSF11 at 10 μg/mL (100 μL/well) can bind human TNFRSF11B-His and the EC₅₀ is 6.0-14.1 ng/mL. The bioactivity of hRANKL was determined by measuring the ability of hRANKL to induce TRAP activity in Raw 264.7 cells and the ED₅₀ is 16 ng/mL.

Human

HEK293

N-mFc

O14788-2 (G63-D244)

8600  [NCBI]

50-60 kDa

Greater than 90% as determined by reducing SDS-PAGE.

Lyophilized powder.

Lyophilized from a 0.2 μm filtered solution of PBS, pH 7.4. Normally 5 % - 8 % trehalose, mannitol and 0.01% Tween 80 are added as protectants before lyophilization.

<1 EU/μg, determined by LAL method.

It is not recommended to reconstitute to a concentration less than 100 μg/mL in ddH₂O.

Stored at -20°C. After reconstitution, it is stable at 4°C for 1 week or -20°C for longer. It is recommended to freeze aliquots at -20°C or -80°C for extended storage.

Room temperature in continental US; may vary elsewhere.

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  [2]. Li B, et al. Roles of the RANKL-RANK Axis in Immunity-Implications for Pathogenesis and Treatment of Bone Metastasis. Front Immunol. 2022 Mar 21;13:824117.  [Content Brief]

  [3]. Tobeiha M, et al. RANKL/RANK/OPG Pathway: A Mechanism Involved in Exercise-Induced Bone Remodeling. Biomed Res Int. 2020 Feb 19;2020:6910312.  [Content Brief]

  [4]. Mikami S, et al. Increased RANKL expression is related to tumour migration and metastasis of renal cell carcinomas. J Pathol. 2009 Aug;218(4):530-9.  [Content Brief]

  [5]. Peng X, et al. Differential expression of the RANKL/RANK/OPG system is associated with bone metastasis in human non-small cell lung cancer. PLoS One. 2013;8(3):e58361.  [Content Brief]

  [6]. Lloyd SA, et al. Soluble RANKL induces high bone turnover and decreases bone volume, density, and strength in mice. Calcif Tissue Int. 2008 May;82(5):361-72.  [Content Brief]