# Aberrant BMP2 signaling during aging and its impact on Women Health

> **NIH NIH P20** · UNIVERSITY OF DELAWARE · 2024 · $311,051

## Abstract

Proper bone maintenance and bone structure is crucial for women health. Osteoporosis and low bone mineral
density have a tremendous negative impact on the physical, emotional, and mental wellbeing of postmenopausal
women. One out of two women will be diagnosed with Osteoporosis in their lifetime. More women die from
osteoporosis each year than die from breast cancer and ovarian cancer
combined.
Bone Morphogenetic Protein 2 (BMP2) is a growth factor that is essential for osteogenesis, increases osteoblast
activity and enhances bone formation. BMP2 is explored as a treatment option for fracture healing and bone
diseases. Although, BMP2 is effective in multiple animal models, it is less successful in the clinic. The response
of patients to BMP2 shows several side effects and BMP2 is not very effective as a treatment.
We recently identified the interaction of Casein Kinase II (CK2) with the BMP Receptor Type Ia (BMPRIa). We
developed a peptide, namely CK2.3, that releases CK2 from the receptor and activates BMP2 signaling in the
absence of BMP2. CK2.3 is more specific compared to BMP2 by activating only a subset of the BMP2 signaling
pathways. Knockout of BMPRIa by CRISPR/CAS, demonstrates that CK2.3 signals through BMPRIa. CK2.3
specifically induces bone formation by driving osteogenesis and increasing osteoblast activity while decreasing
osteoclastogenesis and osteoclast activity.
BMP2 signaling is aberrant in osteoblasts from patients diagnosed with Osteoporosis (POP). Osteoblasts or
explants isolated from femoral heads of POP do not respond to BMP2 by increasing markers for osteoblast
activity and mineralization. However, CK2.3 treatment of osteoblasts from POP leads to an increase in
mineralization. At the same time CK2.3 decreases osteoclastogenesis and osteoclast activity. The goal of this
proposal is to determine the cause of the lack of responsiveness of osteoblasts to BMP2 while they still respond
to CK2.3. Osteoblasts from POP overexpress BMPRIa, followed by downregulation after BMP2 stimulation.
However, the BMP2 signaling pathway downstream of the receptor is not activated. These data suggest that the
problem is localized to BMPRIa shuttling on the plasma membrane, degradation, or recycling. Since CK2.3 acts
through BMPRIa and still activates the signaling pathway, we will define the role of CK2.3 in overcoming the lack
in BMPRIa signaling. BMP2 is an essential growth factor in osteogenesis and bone formation. Understanding
the pathways identified in this proposal is crucial to define new dogmas in bone biology and develop new
successful treatments for bone diseases. Further, CK2.3 by itself may be a potential therapeutic.

## Key facts

- **NIH application ID:** 10954148
- **Project number:** 3P20GM139760-04S3
- **Recipient organization:** UNIVERSITY OF DELAWARE
- **Principal Investigator:** DAWN M ELLIOTT
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $311,051
- **Award type:** 3
- **Project period:** 2021-02-15 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10954148

## Citation

> US National Institutes of Health, RePORTER application 10954148, Aberrant BMP2 signaling during aging and its impact on Women Health (3P20GM139760-04S3). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10954148. Licensed CC0.

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