# Cbf mediates articular cartilage regeneration and repair in aging

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 2022 · $416,909

## Abstract

The long term goal of this study is to develop a safer and more effective therapeutic approach to cure aging-
associated osteoarthritis (OA). The immediate goal of this study is to characterize the mechanism underlying
how core-binding factor beta (Cbfβ) mediates articular cartilage regeneration and repair in aging-associated
OA. Current therapeutic options for aging-associated OA are still limited to pain management and surgical
intervention representing a significant concern in the aging population. Recent studies have shed light on the
nature of OA genetic susceptibility and confirmed a number of candidate genes involved in damage of the
articular cartilage, including Sox9, YAP, Wnt/β-catenin signaling and TGFβ/BMP signaling. However, the root
causes of the disease remain unclear. In our preliminary studies, we found that the expression of Cbfβ
decreases with age in mouse articular cartilage, while postnatal induced chondrocyte-specific Cbfβ-deficient
mice developed spontaneous OA-like phenotype characterized by articular cartilage degradation and
subchondral bone intrusion, which was exacerbated with age. Notably, heatmap analysis of RNA-seq data
showed that Cbfβf/fCol2α1-Cre and aging mice articular cartilage share very similar changes in the gene
expression profiles compared with that of two-month-old mouse articular cartilage. Our qPCR data confirmed
that the OA related gene expression changes in articular cartilage of aging-associated and Cbfβ deficiency
induced OA included downregulated Sox9, BMP7, ALK3 and upregulated Yap, Wnt5a/b, Wnt/β-catenin
BMP2/4. In addition, AAV-CMV-Cbfβ mediated Cbfβ overexpression with local administration protected against
surgical OA in mice. Based on our preliminary data, we hypothesize that deficiency of Cbfβ is one of the main
causes of articular cartilage degeneration in aging-associated osteoarthritis (OA), and Cbfβ enhances articular
cartilage regeneration and repair by modulating multiple key signaling pathways, including Wnt/β-catenin,
BMP/TGFβ, YAP and Sox9 signaling pathways. We will test this hypothesis through three specific aims. In
Aim1, We determine the roles of Cbfβ in articular cartilage regeneration and repair in aging-associated
osteoarthritis through analyses of adult and aged Cbfβf/fAggrecan-CreER mice, and aged wild type mice in
physiological and pathological conditions via a loss-of-function approach. In Aim 2, we characterize the
function of Cbfβ in articular cartilage regeneration and repair and preventing OA genesis in adult and aged
mice via a gain-of-function approach using AAV-CMV-Cbfβ and CbfβOEf/fAggrecan-CreER gene
overexpression models. We will dissect the mechanism underlying how Cbfβ enhances articular cartilage
regeneration and repair by regulating the Wnt/β-catenin, BMP/TGFβ, YAP, and Sox9 signaling pathways in
aging-associated OA in Aim 3. Insights gained from the proposed study will not only address the basic
scientific question about the pathogenesis of aging-associate...

## Key facts

- **NIH application ID:** 10430288
- **Project number:** 5R01AG056438-04
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Wei Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $416,909
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10430288

## Citation

> US National Institutes of Health, RePORTER application 10430288, Cbf mediates articular cartilage regeneration and repair in aging (5R01AG056438-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10430288. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*