# A Neuronal Basis for the Osteocalcin Regulation of Bone Mass

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $376,486

## Abstract

Project Summary
The existence of a neuronal control of bone mass has received over the years many confirmations of various
kind. Although those are by no means the only example of neuronal control of bone mass, the sympathetic
nervous system inhibits bone mass accrual by hampering bone formation whereas the parasympathetic nervous
system favors bone mass accrual. However, neuronal of regulation of bone mass accrual has never been
explored as a possible means to explore bone mass phenotype caused by the absence of various osteoblast-
derived proteins. Likewise, more often than not the importance of neuronal control of bone mass has not been
studied in the craniofacial region. This is surprising since many osteoblasts in bones of the skull and face
originate from neural crest cells. Osteocalcin is the most abundant non-collagenous protein of the bone
extracellular matrix, the absence of which results in a poorly understood high bone mass phenotype. Osteocalcin
is also an hormone and in that capacity it favors, following its binding to as novel receptor described in this
application, the synthesis of catecholamine in the brain and thereby the activity of the sympathetic nervous
system centrally. Independently of this function, as shown in another set of preliminary result of this application,
osteocalcin signals through its first receptor described, Cyprc6a, to inhibit the activity of the parasympathetic
nervous system. Both types of regulation of the autonomic nervous system by osteocalcin could hamper bone
mass accrual. Hence, these preliminary data provide two possible mechanisms to explain what has never been
explained until now: the high bone mass phenotype seen in mice lacking osteocalcin. We intend to address this
question by studying the regulation of bone mass by osteocalcin in the craniofacial region, as well as in the rest
of the skeleton. The Specific Aims of this application are:
  To determine whether an inactivation of Gpr158 in the forebrain will result in a high bone mass by
 decreasing the sympathetic tone.
  To determine whether an inactivation of Gprc6a in post-ganglionic parasympathetic neurons will result in
 a high bone mass phenotype.
  To test through rescue and genetic epistasis experiments whether osteocalcin regulation of the
 sympathetic and/or parasympathetic tone explains its regulation of bone mass accrual.

## Key facts

- **NIH application ID:** 10455018
- **Project number:** 5R01DE027887-05
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Gerard Karsenty
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $376,486
- **Award type:** 5
- **Project period:** 2018-08-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10455018

## Citation

> US National Institutes of Health, RePORTER application 10455018, A Neuronal Basis for the Osteocalcin Regulation of Bone Mass (5R01DE027887-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10455018. Licensed CC0.

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