Soluble RANKL Osteopenia Animal Model for Rapid Drug Evaluation
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Solution Overview
Problem
Conventional osteopenia animal models are time-consuming to develop and evaluate, making it difficult to assess the effectiveness of drugs for bone resorption suppression and osteogenesis promotion due to indirect osteoclast activation and estrogen depletion-induced osteopenia.
Innovation Solution
Administering soluble RANKL or a fused protein of soluble RANKL with an epitope tag to non-human animals to directly activate osteoclasts, inducing osteopenia rapidly, allowing for a more efficient evaluation of osteoclast inhibitors and bone mass increase drugs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional osteopenia models are prepared by methods involving ovariectomy, low-calcium diet, neurectomy, or immobilization, then osteopenia is induced indirectly through estrogen depletion or PTH increase, but it takes approximately 1 to 4 weeks to develop osteopenia, making drug evaluation time-consuming
Solution Approach 1:
The patent extracts and isolates the key factor (RANKL) that directly controls osteoclast differentiation and bone resorption, separating it from the complex indirect mechanisms of conventional models. By administering recombinant RANKL protein directly, the model bypasses the need for ovariectomy-induced estrogen depletion or other indirect pathways, achieving direct osteoclast activation and rapid osteopenia development within days rather than weeks
Solution Approach 2:
The patent performs preliminary action by pre-developing and characterizing the recombinant RANKL protein expression system before applying it to animal models. The RANKL protein is expressed, purified, and validated for osteoclast-inducing activity in advance, allowing immediate administration to animals without requiring time-consuming model development procedures
2Reliability
If conventional osteopenia models use indirect osteoclast activation through estrogen depletion or PTH increase, then the mechanism is complex and involves multiple factors, but it is difficult to demonstrate in which phase of osteopenia a drug can be evaluated as being effective
Solution Approach 1:
The patent extracts and isolates the key factor (RANKL) that directly controls osteoclast differentiation and bone resorption, separating it from the complex indirect mechanisms of conventional models. By administering recombinant RANKL protein directly, the model bypasses the need for ovariectomy-induced estrogen depletion or other indirect pathways, achieving direct osteoclast activation and rapid osteopenia development within days rather than weeks
Solution Approach 2:
The patent applies local quality by creating a localized and controlled osteopenia model where RANKL is administered specifically to target osteoclasts. This localized approach allows precise control over the osteopenia induction process and enables clear demonstration of drug effectiveness at specific phases of bone resorption
Data Source
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AI summary
The present invention provides a method for producing an osteopenia animal model by RANKL administration and an osteopenia animal model. Also, a method for producing an osteopenia animal model, comprising administering, soluble RANKL or a fused protein of soluble RANKL with an epitope tag to a non-human animal so as to promote in vivo osteoclast differentiation and activation in the non-human animal, and an osteopenia animal model produced by the method are provided.