# Investigating modes of cartilage cell size regulation and fate during endochondral ossification

> **NIH NIH F32** · HARVARD MEDICAL SCHOOL · 2021 · $2,500

## Abstract

PROJECT SUMMARY / ABSTRACT
 The skeleton is an essential part of vertebrate anatomy, serving to protect vital soft tissues and organs, as
well as a functional system allowing for stability and movement. The development and maintenance of skeletal
elements requires coordinated interactions between tissue types of diverse origin and function. Understanding
the mechanisms underlying these biological processes is essential to both our understanding of how the body
develops and for clinical interventions in response to malformations or injuries. Cartilage is crucial to the
development of skeletal features, laying down models as the foundation of future bone. Differentiated cartilage
cells, or chondrocytes, undergo cellular hypertrophy to rapidly increase cellular size as a means to facilitate
elongation of the limbs. Hypertrophic chondrocytes also serve in unique and important capacities in developing
vasculature and recruiting hematopoietic stem cells to produce blood cells. Despite their importance in multiple
developmental processes, the cellular mechanisms underlying chondrocyte hypertrophy are not well
understood. The objective of this proposal is to understand how hypertrophic chondrocytes undergo cellular
changes over the course of skeletal development. In order to answer this fundamental biological question, the
following aims are proposed: 1) Characterize the fate of hypertrophic chondrocytes using a live-imaging
approach; 2) Investigate modes of hypertrophy in chondrocytes exhibiting different cellular fates. This
study will employ a novel imaging system (Stimulated Raman Scattering microscopy) to quantify dry-mass
density within hypertrophic chondrocytes in the intact growth plate, thereby characterizing modes of cell size
increase during endochondral ossification. Further, I will use ex vivo imaging of live explants to perform a
longitudinal study of hypertrophic chondrocyte-to-osteoblast transdifferentiation. The ability of differentiated
cells to transition to other lineages is a largely unexplored biological phenomenon and will be of interest across
broader disciplines. Taken together, the insight gained from this work will lead to a clearer understanding of
cell size regulation in hypertrophic chondrocytes and their influence on the development of bone. Importantly,
this work will inform on cellular mechanisms relevant to human health by clarifying the role of hypertrophic
chondrocytes in patterning, growth and maintenance of the skeletal system, which will be applicable both for
developmental abnormalities as well as injury repair.

## Key facts

- **NIH application ID:** 10402435
- **Project number:** 3F32AR076187-03S1
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Amanda K Powers
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,500
- **Award type:** 3
- **Project period:** 2019-07-10 → 2022-07-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10402435

## Citation

> US National Institutes of Health, RePORTER application 10402435, Investigating modes of cartilage cell size regulation and fate during endochondral ossification (3F32AR076187-03S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10402435. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*
