sRANKL Human, GST
Description
Mechanism of Action
sRANKL Human, GST binds to RANK receptors, activating signaling pathways that drive osteoclast differentiation and bone resorption. Key effects include:
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Rapid induction of osteoclastogenesis (within 24–50 hours in mice) .
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Dose-dependent bone mineral density (BMD) reduction, mimicking osteoporosis .
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Elevated serum markers of bone turnover (e.g., TRAP-5b, CTx, calcium) .
Osteoporosis Modeling
sRANKL Human, GST enables rapid bone loss induction in rodents, outperforming traditional ovariectomy (OVX) models in speed and simplicity:
Drug Evaluation
The model has validated therapeutics:
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Anti-RANKL monoclonal antibodies: Neutralizing antibodies (e.g., denosumab analogs) blocked bone loss in 10 days .
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Parathyroid hormone (PTH): Anabolic effects observed in 2 weeks .
Hypercalcemia and Threshold Effects
sRANKL Human, GST administration revealed a critical threshold for hypercalcemia:
| Model | sRANKL (ng/mL) | Phenotype |
|---|---|---|
| Ad-sRANKL (High dose) | 1500 | Severe osteoporosis, hypercalcemia |
| sRANKL-Tg mice | 30 | Osteoporosis without hypercalcemia |
| GST-RANKL injection | 3.5 | Osteoporosis |
| Data from |
Serum sRANKL levels exceeding ~30 ng/mL were required to induce hypercalcemia, suggesting distinct thresholds for bone resorption and calcium dysregulation .
Production and Quality Control
Advantages Over Alternatives
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Speed: Bone loss models established in ≤50 hours vs. weeks for OVX .
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Versatility: Applicable to multiple species (mice, rats) and genders .
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Mechanistic clarity: Direct RANKL-RANK interaction without confounding hormonal changes .
Limitations and Considerations
Product Specs
Product Science Overview
The human recombinant sRANKL fused with a Glutathione S-Transferase (GST) tag is produced in E. coli. This recombinant protein is a single, non-glycosylated polypeptide with a molecular mass of approximately 47 kDa . The GST tag aids in the purification process, making it easier to isolate the protein using affinity chromatography techniques .
RANKL is essential for the formation, function, and survival of osteoclasts, which are cells responsible for bone resorption. It binds to its receptor, RANK, on the surface of osteoclast precursors, promoting their differentiation into mature osteoclasts . This interaction is critical for maintaining bone homeostasis and remodeling.
In addition to its role in bone metabolism, RANKL is involved in the immune system. It is expressed by T cells and plays a role in the development of lymph nodes and the regulation of immune responses .
The recombinant form of sRANKL with a GST tag is widely used in research to study its biological functions and interactions. It is particularly valuable in:
- Bone Metabolism Studies: Understanding the mechanisms of bone diseases such as osteoporosis and rheumatoid arthritis.
- Cancer Research: Investigating the role of RANKL in cancer metastasis, especially in bone metastasis.
- Immunology: Exploring the functions of RANKL in immune cell regulation and lymph node development .
