# Mechanotransduction in Meniscus Health and Repair

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $396,890

## Abstract

ABSTRACT.
Meniscal injuries are a significant clinical problem as each year 850,000 meniscal surgeries are performed in the
United States and nearly twice as many worldwide. Meniscal tears in the avascular inner zone of the tissue do
not heal well with suturing or conservative treatments and can ultimately lead to the development of osteoarthritis
(OA). Therefore, new strategies are needed to enhance endogenous meniscus repair and tissue regeneration.
The menisci play a critical biomechanical role in the knee, providing load support, joint stability, and congruity.
Meniscus tissue is maintained through a balance of anabolic and catabolic activities of meniscus cells. These
cellular activities are controlled not only by biochemical factors in the joint but also by physical factors associated
with joint loading. Mechanobiology, which is the influence of mechanical factors on the biologic response of cells,
is important in converting physical signals into metabolic and inflammatory responses in meniscus. However,
the mechanisms by which mechanical signals are transduced in meniscus cells have yet to be identified. Our
overall goal is to identify critical meniscus mechanotransduction pathways and modulate these
pathways to promote meniscus repair and prevent OA development.
Our work has shown that transient receptor potential vanilloid 4 (TRPV4) is a critical component in cartilage
mechanotransduction and metabolism. The activation of TRPV4 can block IL-1 induced catabolic responses and
also increases cell migration and proliferation, which are important processes to enhance tissue repair. While
we have found that TRPV4 is expressed in the meniscus, the function of this mediator in meniscus health and
disease is currently unknown. In this proposal, we will determine how mechanotransduction occurs through
TRPV4 in meniscus and identify modulators of this pathway that will be used to enhance tissue repair and prevent
OA development. We hypothesize that mechanotransduction by TRPV4 plays a key role in meniscus metabolism
and can be modulated to enhance meniscus repair and prevent the development of OA. In this proposal, we will
determine the effects of mechanical stimulation on TRPV4-mediated metabolism in healthy meniscus cells.
Next, we will elucidate alterations in TRPV4-mediated mechanotransduction pathways in meniscus pathology.
Finally, we will enhance integrative meniscus repair and prevent the development of OA by modulation of
mechanotransduction pathways. In this proposal, we will identify the key signaling pathways downstream of
TRPV4 that may function as novel drug targets to 1) treat patients with immobilized joints to simulate exercise
and maintain joint health; 2) enhance meniscus tissue regeneration using tissue engineering strategies; and 3)
enhance meniscus repair and prevent the development of OA. Novel therapeutic targets identified in this
proposal can subsequently be developed into drugs to enhance meniscus repair and prevent the d...

## Key facts

- **NIH application ID:** 9850532
- **Project number:** 5R01AR073221-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Amy L McNulty
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $396,890
- **Award type:** 5
- **Project period:** 2019-01-15 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850532

## Citation

> US National Institutes of Health, RePORTER application 9850532, Mechanotransduction in Meniscus Health and Repair (5R01AR073221-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9850532. Licensed CC0.

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