# PTH Attenuation of Spinal Degeneration During Aging PI Janet Crane

> **NIH NIH P01** · JOHNS HOPKINS UNIVERSITY · 2021 · $288,095

## Abstract

SUMMARY
Low back pain is the leading cause of disability, driven predominantly by aging. Pain contributes to frailty by
lowering quality of life and limiting physical activities. Intervertebral disc (IVD) degeneration is the most common
cause of low back pain, but is a non-specific finding. No cause-directed, mechanism-based medications protect
the spine from progression of degeneration and pain. The spine is a complex joint, built from alternating bony
vertebrae and IVD. The vertebral endplate forms a structural boundary between the IVD and the vertebral body.
Recent studies have implicated that the vertebral endplate plays a key role in the development of spinal
degeneration and low back pain. We have recently reported that daily administration of parathyroid hormone
(PTH) in aged mice for two months increases IVD cell size, restoring the vacuoles and rejuvenating the IVD. We
have also found that cartilaginous endplates become ossified and porous during aging, which induces sensory
innervation for spinal hypersensitivity. Our preliminary data demonstrates that endplate sclerosis improves with
PTH administration. Most importantly, we have found that the aberrant innervation of the endplate is reversed
with PTH and is associated with a reduction in pain behaviors in the IVD mouse models. We hypothesize that
PTH stimulated anabolic bone formation remodels the sclerotic, porous EP to reduce aberrant nociceptive
innervation. In this project, we will pursue the following specific aims: Aim 1: Examine vertebral endplate
remodeling in the process of PTH-induced rejuvenation of IVD; Aim 2: Identify cellular target of PTH-induced
remodeling of porous vertebral endplates; and Aim 3: Determine the mechanism of PTH-induced reduction of
sensory innervation and improved pain behaviors. Our study team is comprised of basic scientists with expertise
in bone biology regarding PTH cell signaling mechanisms and neuroscience regarding nociceptor neuronal
activity, as well as, physician-scientists with translation expertise in mouse models of human disease, spinal
degeneration, and clinical use of PTH. We are uniquely suited to further understand the mechanistic actions of
PTH and potential as a disease modifying treatment of low back pain. Understanding the mechanism of PTH
treatment of low back pain will provide necessary data to inform further drug development and clinical trial
designs exploring activation of the PTH signaling pathway as a disease-modifying treatment of spinal
degeneration.
.

## Key facts

- **NIH application ID:** 10090197
- **Project number:** 1P01AG066603-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Janet Crane
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $288,095
- **Award type:** 1
- **Project period:** 2021-01-15 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10090197

## Citation

> US National Institutes of Health, RePORTER application 10090197, PTH Attenuation of Spinal Degeneration During Aging PI Janet Crane (1P01AG066603-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10090197. Licensed CC0.

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