# Cellular metabolism at the crossroads of skeletal regeneration

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 2022 · $350,944

## Abstract

Limb regeneration after injury is a sophisticated and energetically expensive process. In this process, progenitor
proliferation, osteoblast differentiation and mineral deposition all require sufficient supplies of biological building
blocks and ATP(1-5). However, the contribution of cell metabolism and its genetic control of skeletal regeneration
is largely unknown, representing a major knowledge gap. Using the established mouse digit tip amputation
model, we found that mice exhibit impaired regeneration during aging, and that this impairment is linked to
increased expression of glycolysis and oxidative phosphorylation (OxPhos) genes, compared to young mice.
These exciting preliminary results have led us to investigate the metabolic and genetic mechanisms that underlie
skeletal regeneration.
Our preliminary findings support that skeletal regeneration is metabolism-dependent and can be manipulated by
exogenous metabolites and gene expression, respectively. These data suggest that administration of
oxaloacetate (OAA), a pro-glycolytic and pro-respiratory metabolite, increases regenerated bone volume and
thickness in a mouse model. Alternatively, modulation of collagen triple helix repeat containing 1 (Cthrc1) also
alters skeletal regeneration. Cthrc1 is specifically expressed in the blastema, the dedifferentiated tissue structure
central to regeneration, and Cthrc1-/- mice demonstrated impaired regeneration and dysregulated cell
metabolism. Moreover, our preliminary data show that treatment with OAA increases Cthrc1 expression,
reinforcing a direct link between metabolism and genetic control. We hypothesize that a finely tuned interaction
between cell metabolism and genetic control synergistically regulates cell function, and that this interaction can
be manipulated both exogenously (OAA) and at a gene level (Cthrc1) to modulate regenerative outcomes.

## Key facts

- **NIH application ID:** 10529832
- **Project number:** 1R01HD107034-01A1
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Mimi C Sammarco
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $350,944
- **Award type:** 1
- **Project period:** 2022-09-07 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10529832

## Citation

> US National Institutes of Health, RePORTER application 10529832, Cellular metabolism at the crossroads of skeletal regeneration (1R01HD107034-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10529832. Licensed CC0.

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