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HOXA10 promotes Gdf5 expression in articular chondrocytes
Tomohiko Murakami1, Lerdluck Ruengsinpinya2, Yoshifumi Takahata3
1Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, 1-8 Yamada-Oka, Suita, Osaka, 565-0871, Japan. murakami.tomohiko.dent@osaka-u.ac.jp.
Scientific Reports
|December 20, 2023
Summary
Homeobox A10 (HOXA10) directly regulates Growth Differentiation Factor 5 (GDF5) expression in articular cartilage. This finding is crucial for understanding joint development and osteoarthritis pathogenesis.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Growth Differentiation Factor 5 (GDF5) is vital for articular cartilage homeostasis and joint development.
- GDF5 gene variations are linked to osteoarthritis (OA) risk.
- Understanding GDF5 regulation is key to addressing OA.
Purpose of the Study:
- To identify transcription factors regulating GDF5 expression in articular cartilage superficial zone (SFZ) cells.
- To elucidate the role of HOXA10 in GDF5 gene regulation.
Main Methods:
- Microarray analysis to identify SFZ-specific transcription factors.
- Generation of Gdf5-HiBiT knock-in (KI) mice for GDF5 expression monitoring.
- CRISPR/Cas9 genome editing.
- In vitro overexpression and knockdown experiments.
- Chromatin immunoprecipitation (ChIP) and promoter assays.
Main Results:
- Eleven transcription factors highly expressed in SFZ cells were identified.
- HOXA10 was found to upregulate GDF5 expression in SFZ cells.
- HOXA10 directly binds to and regulates the Gdf5 gene promoter.
- Gdf5-HiBiT KI mice provide a reliable method for GDF5 expression monitoring.
Conclusions:
- HOXA10 plays a significant role in regulating GDF5 expression in articular cartilage.
- The Gdf5-HiBiT KI mouse model is a valuable tool for studying GDF5 regulation and function.
- Findings contribute to understanding the molecular mechanisms underlying joint development and OA.
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