Osteoblastic sclerostin loop3-LRP4 interaction could be required by sclerostin to inhibit bone formation

Project: Research project

Project Details

Description

Sclerostin has become a novel bone anabolic target. Humanized therapeutic sclerostin antibody romosozumab which mainly targeted sclerostin loop2 was demonstrated to promote bone formation for postmenopausal osteoporosis. However, severe cardiac ischemic events found in clinical trials of romosozumab significantly limited its clinical use. Together, it was hypothesized that osteoblastic sclerostin loop3-LRP4 interaction could be required by sclerostin to inhibit bone formation. To test the hypothesis using the above established genetic mouse models and pharmacologic peptide tool, we have the following two specific Aims: Aim 1. To genetically determine the role of osteoblastic sclerostin loop3-LRP4 interaction in the antagonistic effect of sclerostin on bone formation. Aim 2. To pharmacologically determine the role of sclerostin loop3-LRP4 interaction in the antagonistic effect of sclerostin on bone formation.
StatusActive
Effective start/end date1/01/2531/12/27

UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This project contributes towards the following SDG(s):

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

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