RANKL/TNFSF11 Protein, Human

RANKL (TNFSF11), a type II transmembrane protein, is receptor activator of NF-κB (RANK) ligand. RANKL is an activator of RANK. When binding to RANK, 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 is a recombinant human RANKL (I140-D317) without any tag, which is produced in E.coli^[1][2].

RANKL (TNFSF11) belongs to TNF family. RANKL is a type II transmembrane protein and is a receptor activator of NF-κB (RANK) ligand. RANKL is an activator of RANK. RANKL binds to RANK 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^[1]. RANKL is also expressed by T cells and increases proliferation and survival of dendritic cells^[2].
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^[1][3].
RANKL is critical for osteoclasts maturation, bone modeling, and bone remodeling, as well as the development of lymph nodes (LNs)^[1].

RANKL (human, 0-50 ng/mL, 24 h) stimulates migration of a clear cell RCC cell line, Caki-1^[4].
RANKL (human, 24 h) stimulates PAa cell migration and invasion^[5].

RANKL (human, 0.4 or 2 mg/kg/day, s.c.) induces high bone turnover and decreases bone volume, density, and strength in C57BL/6J female mice^[6].

1.The ED₅₀ is <3.23 μg/mL μg/mL as measured by ELISA.
2.Measured by its binding ability in a functional ELISA. When Recombinant Human RANK/TNFRSF11A Protein is coated at 0.5 μg/mL (100 μL/well) can bind Recombinant Human RANKL/TNFSF11. The ED₅₀ for this effect is 7.413 ng/mL.

Human

E. coli

Tag Free

O14788-1 (I140-D317)

8600  [NCBI]

IRAEKAMVDGSWLDLAKRSKLEAQPFAHLTINATDIPSGSHKVSLSSWYHDRGWAKISNMTFSNGKLIVNQDGFYYLYANICFRHHETSGDLATEYLQLMVYVTKTSIKIPSSHTLMKGGSTKYWSGNSEFHFYSINVGGFFKLRSGEEISIEVSNPSLLDPDQDATYFGAFKVRDID

Approximately 20 kDa

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

Lyophilized powder

Lyophilized from a 0.2 μm filtered solution of 20 mM Tris-HCl, 150 mM NaCl, pH 8.0 or PBS, pH 8.0.

<1.0 EU/μg, determined by LAL method.

It is not recommended to reconstitute to a concentration less than 100 μg/mL in ddH₂O. For long term storage it is recommended to add a carrier protein (0.1% BSA, 5% HSA, 10% FBS or 5% Trehalose).

Stored at -20°C for 2 years. After reconstitution, it is stable at 4°C for 1 week or -20°C for longer (with carrier protein). It is recommended to freeze aliquots at -20°C or -80°C for extended storage.

Room temperature in continental US; may vary elsewhere.

• [1]. Ono T, et al. RANKL biology: bone metabolism, the immune system, and beyond. Inflamm Regen. 2020 Feb 7;40:2.  [Content Brief]

  [2]. Hofbauer LC, et al. Role of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin in bone cell biology. J Mol Med (Berl). 2001 Jun;79(5-6):243-53.  [Content Brief]

  [3]. 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]

  [4]. 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]

  [5]. 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]

  [6]. 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]

  [7]. 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]