# The essential roles of primary cilia in heterotopic ossification

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2024 · $410,535

## Abstract

PROJECT SUMMARY/ABSTRACT
Heterotopic ossification (HO), a diverse pathologic process of formation of extraskeletal bone in muscle and
soft tissues, can be classified into hereditary and nonhereditary (acquired) HO types. A rare and devastating
form of hereditary HO is fibrodysplasia ossificans progressiva (FOP), caused by gain-of-function mutations in
Activin receptor A type I (Acvr1) gene. In the nonhereditary forms, HO frequently occurs in tendons and
ligaments and is commonly incited upon soft tissue trauma, orthopedic surgeries, combat-related blasts, and
burns. There are currently still no effective drugs to treat HO. Our long-term goal is to decipher the
mechanism(s) of HO and develop novel strategies for the clinical treatment of HO. The overall objectives are to
(i) elucidate the essential roles of cilia on the Bone morphogenetic protein (BMP) signaling pathway and (ii)
determine its function using novel HO models. The central hypothesis is that primary cilia play central roles in
transducing normal and pathogenic BMP signaling and regulating the pathophysiological mechanism of both
hereditary and nonhereditary HO. The rationale is that both hereditary and nonhereditary HO formation are
primarily mediated by the BMP signaling pathway. However, it remains elusive where and how BMP signaling
is transduced and regulated in cells. Primary cilia are antenna-like structures protruding from the surface of
cells and are critical for proper transduction of many cellular signaling pathways. Dysfunctional primary cilia
result in a broad spectrum of human diseases collectively termed ciliopathies. Our preliminary data suggest
that primary cilia play central roles in transducing normal and pathogenic BMP signaling and regulate the
pathophysiological mechanism(s) of HO formation. The central hypotheses will be tested by pursuing these
specific aims: 1) Determine the ciliary components/pathways that govern normal and pathogenic BMP
signaling pathways. 2) Determine the regulatory function of cilia in our newly established nonhereditary
burn/tenotomy-induced HO mouse models that have abrogated ciliary signaling pathways. 3) Identify targets
for inhibition of cilium-related pathways as the basis for treatments in hereditary HO and nonhereditary HO.
The research proposed in this application is innovative because our preliminary data suggest that FOP and
perhaps other HO conditions represent cilium-mediated disorders, which provides a novel perspective for
future therapies. Mechanistically, we will systematically elucidate the function of cilia on BMP signaling
specifically as associated with HO mouse models. The proposed research is significant, and scientifically it will
build a new paradigm that primary cilium plays a central role in transducing BMP signaling in chondrogenesis
and/or osteogenesis that ultimately results in both hereditary and nonhereditary HO. Clinically, targeting the
cilia-mediated BMP pathway is an unexplored therapeutic strategy that ...

## Key facts

- **NIH application ID:** 10916502
- **Project number:** 5R01AR081318-02
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Haitao Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $410,535
- **Award type:** 5
- **Project period:** 2023-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10916502

## Citation

> US National Institutes of Health, RePORTER application 10916502, The essential roles of primary cilia in heterotopic ossification (5R01AR081318-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10916502. Licensed CC0.

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