# Mechanisms of Primary Cilia Regulating Tendon Enthesis Development and Regeneration

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $550,096

## Abstract

PROJECT SUMMARY
40% of the population over the age of 60 experiences a rotator cuff tear. The high failure rates of rotator cuff tear
after surgical repair or non-surgical treatment make it a major clinical challenge. The outcome failures
accompany the formation of scar tissues at the tendon-to-bone insertion (tendon enthesis) with disorganized
architecture and deteriorated function. Development of effective therapeutics has been hampered by limited
knowledge of enthesis development biology and mechanobiology and an incomplete understanding of
endogenous mechanisms governing enthesis pathogenesis and healing. To bridge this knowledge gap, the
current proposal seeks to elucidate how tendon enthesis responds to its mechanical and biochemical
environment during development and healing processes. It is known that a combination of mechanical force and
distinct pathways, including hedgehog (Hh) signaling, drive enthesis formation, promote remodeling of mature
enthesis, and affect enthesis healing. Recently, our studies have indicated that the primary cilium, a solitary
antenna protruding from mammalian cell surface, potentially functions as a hub for mechanotransduction and
Hh signaling. Building on our previous work, the objective of this proposal is to gain a mechanistic understanding
of the role of primary cilia in concentrating and synchronizing mechanical and Hh signals during enthesis
development and healing. To achieve this objective, we will determine identities and activities of ciliated enthesis
cells during enthesis development and mechanical adaptation (Specific Aim 1) and evaluate the regenerative
capacity of ciliated enthesis cells for improving enthesis healing (Specific Aim 2). The approaches we will use
include cilia-labeled and cilia-deleted transgenic mouse models, different established loading models, cell
transplantation, and transcriptomics analysis, combined with structural, compositional, and biomechanical
evaluation assays. At the conclusion of this project, we expect to identify new cilia-regulated mechano-
transduction pathways during in vivo enthesis mechanical adaptation and suggest novel mechanisms by which
cilia convert mechanical cues to cellular signaling events. The new findings of the role of primary cilia in enthesis
healing will guide the development of novel pharmacological and mechanobiology therapeutics for treating
rotator cuff tears.

## Key facts

- **NIH application ID:** 10886627
- **Project number:** 5R01AR082797-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Fei Fang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $550,096
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10886627

## Citation

> US National Institutes of Health, RePORTER application 10886627, Mechanisms of Primary Cilia Regulating Tendon Enthesis Development and Regeneration (5R01AR082797-02). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10886627. Licensed CC0.

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