# Mechanism of BMP2 regulation of Mandibular Condylar Cartilage Growth

> **NIH NIH K08** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2020 · $174,291

## Abstract

Abstract
The objective of the proposed research is to understand the role of Bone Morphogenic Protein 2 (BMP2) in the
postnatal growth, pathogenesis and adaptive remodeling of mandibular condylar cartilage (MCC). The long-
term goal of the applicant (PI) is to understand the mechanism regulating the growth and differentiation of
MCC. Temporomandibular joint disorders (TMDs) affect over 15 million Americans and it is estimated that the
United States spends billions of dollars each year on TMDs. Bone Morphogenic Proteins (BMPs) signaling is
crucial for the development and postnatal maintenance of MCC, while overexpression of BMP signaling has
been associated with degenerative disorders of the cartilage. Despite a wealth of literature on BMPs signaling
in articular cartilage of the knee, little is known about BMPs role in postnatal growth, adaptive remodeling and
pathogenesis of MCC. In our MCC loading model we found increased cartilage thickness, increased matrix
synthesis and mineralization, as well as increased hypertrophic differentiation of chondrocytes. Moreover,
conditional deletion of BMP2 in MCC showed decreased synthesis and mineralization of extracellular matrix
and decreased hypertrophic differentiation of chondrocytes. These data suggest that BMP2 regulates MCC
growth and differentiation. However, the mechanisms underlying the regulatory effects of BMP2 in the matrix
synthesis and hypertrophic differentiation of chondrocytes in MCC remain unknown.
Our global hypothesis is that BMP2 is required for postnatal growth and adaptive remodeling of the MCC.
Our understanding is that BMP2 is the master regulator of extracellular matrix synthesis, matrix mineralization
and hypertrophic differentiation of chondrocytes. To test this hypothesis, we propose the following specific
aims:
Specific Aim 1: To determine the effects and mechanism of BMP2 loss of function on MCC and the
subchondral bone. Using a transgenic mice model with lineage specific deletion of BMP2, we will examine the
outcomes of BMP2-loss-of-function on MCC and the subchondral bone.
Specific Aim 2: To determine if the anabolic effect of TMJ loading in young mice is mediated through BMP2
signaling. We will utilize two complementary in vivo mice loading/unloading models, which causes either an
increase or decrease in extracellular matrix mineralization and hypertrophic differentiation of chondrocytes.
Specific Aim 3: The effect of BMP2 loss of function on the Ihh signaling pathway. Using specific activators
and inhibitors in an ex vivo organ culture model we will investigate possible cross-talk between BMP2 and Ihh
signaling in regulating anabolic response in MCC.
Greater understanding of the effect of BMP2 loss-of-function on the postnatal growth and pathogenesis of
MCC will aid in the understanding of the diseases of the TMJ and will help us in translating new approaches to
regenerate the joint.

## Key facts

- **NIH application ID:** 9898162
- **Project number:** 5K08DE025914-04
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Sumit Yadav
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $174,291
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9898162

## Citation

> US National Institutes of Health, RePORTER application 9898162, Mechanism of BMP2 regulation of Mandibular Condylar Cartilage Growth (5K08DE025914-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9898162. Licensed CC0.

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