Osteoblast-Specific Overexpression of Nucleolar Protein NO66 /RIOX1 in Mouse Embryos Leads to Osteoporosis in Adult Mice.
Qin ChenKrishna M SinhaBenoit de CrombruggheRalf KrahePublished in: Journal of osteoporosis (2023)
In previous study, we showed that nucleolar protein 66 (NO66) is a chromatin modifier and negatively regulates Osterix activity as well as mesenchymal progenitor differentiation. Genetic ablation of the NO 66 ( RIOX1 ) gene in cells of the Prx 1-expressing mesenchymal lineage leads to acceleration of osteochondrogenic differentiation and a larger skeleton in adult mice, whereas mesenchyme-specific overexpression of NO 66 inhibits osteochondrogenesis resulting in dwarfism and osteopenia. However, the impact of NO66 overexpression in cells of the osteoblast lineage in vivo remains largely undefined. Here, we generated osteoblast-specific transgenic mice overexpressing a FLAG-tagged NO66 transgene driven by the 2.3 kB alpha -1 type I collagen ( Col1a 1) promoter. We found that overexpression of NO66 in cells of the osteoblast lineage did not cause overt defects in developmental bones but led to osteoporosis in the long bones of adult mice. This includes decreased bone volume (BV), bone volume density (bone volume/total volume, BV/TV), and bone mineral density (BMD) in cancellous compartment of long bones, along with the accumulation of fatty droplets in bone marrow. Ex vivo culture of the bone marrow mesenchymal stem/stromal cells (BMSCs) from adult Col1a1 -NO66 transgenic mice showed an increase in adipogenesis and a decrease in osteogenesis. Taken together, these data demonstrate a crucial role for NO66 in adult bone formation and homeostasis. Our Col1a1 -NO66 transgenic mice provide a novel animal model for the mechanistic and therapeutic study of NO66 in osteoporosis.
Keyphrases
- bone mineral density
- bone marrow
- postmenopausal women
- induced apoptosis
- body composition
- bone regeneration
- transcription factor
- cell cycle arrest
- stem cells
- cell proliferation
- high fat diet induced
- mesenchymal stem cells
- gene expression
- genome wide
- signaling pathway
- dna methylation
- childhood cancer
- endoplasmic reticulum stress
- lipopolysaccharide induced
- cell death
- cell fate
- soft tissue
- skeletal muscle
- type diabetes
- machine learning
- oxidative stress
- artificial intelligence
- atrial fibrillation
- inflammatory response
- lps induced
- metabolic syndrome