# Multiscale mechano-metabolic regulation of fibrous tissue homeostasis

> **NIH NIH F32** · UNIVERSITY OF PENNSYLVANIA · 2024 · $73,828

## Abstract

ABSTRACT
 Meniscus tears are one of the most common knee injuries and often fail to heal in adults. Current surgical
treatments increase osteoarthritis (OA) risk, especially in patients with metabolic syndrome (including obesity,
hyperglycemia, and dyslipidemia). While this is often attributed to mechanical overloading, metabolic syndrome
is also associated with OA in non-weightbearing joints. Preclinical studies suggest elevated inflammatory signals
from adipose tissue (e.g., adipokine dysregulation) mediate articular cartilage degeneration following meniscal
injury. Obesity and OA are associated with aberrant microstructural remodeling and strain attenuation in the outer
meniscus. Despite these findings, the mechano-metabolic mechanisms controlling meniscus cell function remain
unresolved. To address these gaps in knowledge, this proposal will investigate the impact of metabolic syndrome
on meniscus cell mechanoactivation. Our central hypothesis is that persistent adipokine dysregulation
exacerbates degeneration by altering meniscus cell setpoints for mechano-responsivity and perturbing their
response to homeostatic signals. To test this hypothesis, this proposal uses novel, multiscale experimental
techniques to determine if metabolic syndrome impairs transmission of tensional cues in the meniscus.
Specifically, Aim 1 will test if mechano-metabolic interactions alter meniscus cell contractile force generation and
response to static and dynamic microenvironmental cues. Aim 2 will determine how metabolic memory arising
from transient and sustained adipokine dysregulation influences meniscus cell mechanoactivation, phenotype,
and multiscale tissue mechanical properties in response to homeostatic and pathological tensional cues. I
hypothesize that adipokine dysregulation will impair meniscus cell contractile force generation and
mechanoactivation, leading to loss of fibrous phenotype and aberrant matrix remodeling. This work will generate
novel insight into how mechanotransductive and metabolic crosstalk regulates fibrous tissue homeostasis and
direct regenerative strategies for meniscus repair in high-risk patients.

## Key facts

- **NIH application ID:** 10997211
- **Project number:** 1F32AR084906-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Meghan Elizabeth Kupratis
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $73,828
- **Award type:** 1
- **Project period:** 2024-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10997211

## Citation

> US National Institutes of Health, RePORTER application 10997211, Multiscale mechano-metabolic regulation of fibrous tissue homeostasis (1F32AR084906-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10997211. Licensed CC0.

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