# Unraveling Mechanisms Driving Female-Specific Osteogenesis after Disrupting a Brain-to-Bone Circuit

> **NIH NIH K01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $130,424

## Abstract

ABSTRACT
Estrogen is a critical regulator of energy balance and skeletal metabolism. Women spend more than 1/3 of their
lives in an estrogen depleted state; drastically increasing their risk for age-related bone diseases such as
osteoporosis and fractures. Recent work by our lab and others demonstrates that loss of central estrogen
signaling in the arcuate nucleus (ARC) of the hypothalamus results in a female-specific elevation in bone mass
and strength, however molecular mechanisms that govern those responses are still unknown. I hypothesize that
deletion of ERa in the ARC of Esr1Nkx2-1Cre and ERaKOARC female mice releases a humoral brain-dependent
osteogenic factor (BDOF) which inherently changes resident SSCs, fating these cells for osteogenesis, and that
the changed SSCs are sufficient to enhance fracture repair and reverse bone loss in osteoporotic and
aged mouse models. For this project I will 1) use an unstabilized tibia fracture model to ask if Esr1Nkx2-1Cre
females have enhanced fracture repair. 2) I will use my new bioassay to test HPLC/FPLC fractionated mouse
plasma to identify and purify the BDOF, and 3) I will identify the molecular signals driving osteoblast expansion
in female mutants using a mutant-derived SSC transplant model. Answering these questions is critical for
the advancement of therapeutics for bone-related diseases in women and men.

## Key facts

- **NIH application ID:** 10152486
- **Project number:** 5K01AG065916-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Candice Herber
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $130,424
- **Award type:** 5
- **Project period:** 2020-05-01 → 2022-01-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10152486

## Citation

> US National Institutes of Health, RePORTER application 10152486, Unraveling Mechanisms Driving Female-Specific Osteogenesis after Disrupting a Brain-to-Bone Circuit (5K01AG065916-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10152486. Licensed CC0.

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