# Modulating PTOA development with parathyroid hormone

> **NIH NIH R01** · CORNELL UNIVERSITY · 2024 · $389,948

## Abstract

Osteoarthritis (OA) is a joint disease and the major cause of disability in the adult population. Joint pathology
includes disruption of normal cartilage morphology, changes in the underlying subchondral bone properties,
and induction of osteophyte formation at the joint margins. Traumatic joint injuries such as meniscus and
ligament tears or articular cartilage damage increase the susceptibility of developing a specific type of OA,
post-traumatic arthritis (PTOA). The association of PTOA with a joint injury provides a well-defined event after
which to intervene and attenuate or inhibit subsequent OA initiation and development. In addition to cartilage
damage with PTOA, progressive changes to subchondral bone develop that initiate with bone resorption and
loss, suggesting that targeting bone could prevent early-stage PTOA. We have developed a non-invasive
model that induces OA with repetitive loading and PTOA with a single dose of loading applied to the mouse
knee. In our preliminary data with this OA model, intermittent parathyroid hormone (iPTH) was beneficial to
joint tissue health in adult male mice, even when iPTH treatment was followed by 6 weeks of damaging daily
loading. Using the PTOA model, we found that load-induced joint damage was attenuated when bone
remodeling was inhibited immediately after traumatic loading.
 Based on these intriguing results, we hypothesize that intermittent PTH treatment will inhibit the
development of PTOA pathology in the joint. We propose to test this hypothesis using our load-induced PTOA
model in three specific aims:
(Aim 1) To attenuate load-induced tissue morphological damage and cellular responses after a single bout of
damaging in vivo loading with delayed iPTH treatment in adult male and female mice;
(Aim 2) To demonstrate that pain is reduced, joint function maintained and neuroimmune mechanisms
modulated with iPTH treatment immediately or delayed 2 wks after a single bout of damaging in vivo loading to
initiate PTOA in adult male and female mice
(Aim 3) To identify altered neuroimmune gene expression is correlated with reduced tissue damage in
cartilage, synovium and bone from adult male and female mice treated with iPTH immediately after a single
bout of in vivo loading to initiate PTOA
 We expect that the beneficial effects of iPTH will be able to overcome existing tissue damage and
modify PTOA disease progression with delayed treatment through bone anabolism and chondrogenesis. Our
preliminary data demonstrate a role for specifically targeting the subchondral bone and cartilage using FDA-
approved osteoporosis treatments in slowing OA progression. iPTH inhibition of cartilage and bone pathology
following joint trauma will transform clinical practice.

## Key facts

- **NIH application ID:** 10930058
- **Project number:** 5R01AR081943-02
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Marjolein C van der Meulen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $389,948
- **Award type:** 5
- **Project period:** 2023-09-15 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10930058

## Citation

> US National Institutes of Health, RePORTER application 10930058, Modulating PTOA development with parathyroid hormone (5R01AR081943-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10930058. Licensed CC0.

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