# Primary Cilia as Mechanotransducer in Bone

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $345,644

## Abstract

Summary
Hip fractures are the most devastating result of osteoporosis and often the first step in a downward spiral of lost
ambulation and independence, institutionalization, and secondary medical morbidity and mortality. Within one
year of hip fracture, 50% of patients will be unable to walk without assistance, 25% will require long-term care,
and 20% will have died. One potent regulator of bone formation is physical loading (Krahl et al. 1994); however,
the cellular sensing mechanism directing mechanotransduction has proven to be elusive. Our laboratory is one
of the first to demonstrate that the osteocyte primary cilium plays a major role in this process (Malone et al.
2007). The primary cilium is a solitary cellular extension present in virtually every cell in the body, but its function
has yet to be fully characterized. As osteocyte mechanosensors, these organelles act synergistically with other
known regulators of bone metabolism. Our contribution is to elucidate the primary cilium microdomain’s role in
osteocyte mechanotransduction and identify the intracellular signaling mechanisms involved. This contribution
is significant because it catalyzes a continuum of research leading to novel pharmacologic therapeutics that
potentiate mechanical loading at a molecular level. The long-term goal of this project is to determine how primary
cilia contribute to bone mechanosensing and capitalize on this knowledge to develop novel therapies. The overall
objective of this application is to exploit the molecular mechanisms identified in the last funding period to sensitize
osteocyte primary cilia and identify osteocyte-cilia specific therapeutic targets. We will achieve this objective by
establishing the potential of osteocyte cilia therapeutics in vivo (SA1), enhancing osteocyte-specificity through
molecular manipulation of the intraciliary signaling system (SA2), and ensuring that ciliary strategies do not have
adverse effects on bone biology (SA3). At the conclusion of this project, we expect to contribute potential
pharmacologic agents that target unique characteristics of the osteocyte microdomain to bias bone formation
without adverse effects to normal physiology. Osteoporosis prevention will dramatically increase patient quality
of life, reduce morbidity, and cut health care costs. A collateral benefit will be extending this knowledge to
applications in other cell types to develop treatments for numerous cilia-associated diseases.

## Key facts

- **NIH application ID:** 9928898
- **Project number:** 5R01AR062177-09
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** X. Edward GUO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $345,644
- **Award type:** 5
- **Project period:** 2012-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928898

## Citation

> US National Institutes of Health, RePORTER application 9928898, Primary Cilia as Mechanotransducer in Bone (5R01AR062177-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9928898. Licensed CC0.

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