# Bone anabolic effects of osteoclast-produced phospho-Wnt5a

> **NIH NIH R56** · EMORY UNIVERSITY · 2023 · $313,000

## Abstract

Project Summary
There is still a need to identify new efficacious and cost effective anabolic bone drugs to treat osteopenic
conditions, bone fragility and repair. The goal of this application is to establish a phosphorylated form of Wnt5a
produced by osteoclasts as a clastokine, capable of enhancing bone formation in vivo. This comes with the
translational promise to deliver phosphomimetic Wnt5a peptide as an anabolic drug to promote osteogenesis in
the future. The proposed work is premised on our compelling preliminary evidence that conditional deletion of
Wnt5a from osteoclasts (OCLs) resulted in decreased bone mass, which was concomitant with decreased bone
formation rate in vivo. We further discovered a specific Ser phosphorylation of Wnt5a in osteoclastic cells. This
phospho-Wnt5a or its mimetic mutant proteins promoted osteogenesis. We therefore hypothesize that a
phosphorylated form of Wnt5a, produced by OCL but not OBs, serve as a clastokine to promote anabolic
bone formation. To verify this hypothesis, we will: first establish the in vivo control of OB function by OCL-
produced Wnt5a and determine the skeletal consequences of Wnt5a over-expression in OCL-precursors (First
Aim). We will then reveal the cellular and molecular mechanisms via which a post-translationally modified form
of Wnt5a produced by OCL control OB function in vitro and in vivo. Finally, we will generate induced pluripotent
stem cells expressing phospho-defective and -mimetic Wnt5a mutants via genome editing to promote bone
formation in a murine critical sized calvarial defect (Second Aim).

## Key facts

- **NIH application ID:** 10929243
- **Project number:** 1R56AR080718-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Moulay Hicham DRISSI
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $313,000
- **Award type:** 1
- **Project period:** 2023-09-18 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10929243

## Citation

> US National Institutes of Health, RePORTER application 10929243, Bone anabolic effects of osteoclast-produced phospho-Wnt5a (1R56AR080718-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10929243. Licensed CC0.

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