Age-Related Decrease in Pellino-1 Expression Contributes to Osteoclast-Mediated Bone Loss.
Dong Suk YoonSeung Eun OhKyoung-Mi LeeSujin JungEun Ae KoTae-Gyun KimKwang Hwan ParkJin-Woo LeePublished in: Advanced biology (2024)
Aging-related bone loss is driven by various biological factors, such as imbalanced bone metabolism from decreased osteoblast and increased osteoclast activities. Various transcriptional and post-transcriptional factors increase osteoclast activity with aging; however, studies regarding the post-translational regulators of osteoclast activity are still limited. The ubiquitin E3 ligase Pellino-1 is a well-known post-translational regulator of inflammation. However, how Pellino-1 expression regulation affects osteoclast differentiation remains unclear. This study determined that Pellino-1 levels are reduced in bone marrow monocytes (BMMs) from 40-week-old mice compared to 4-week-old mice. Interestingly, conditional Knockout (cKO) of Pellino-1 in 6-week-old mice resulted in decreased bone mass, reduced body size, and lower weight than in Pellino-1 floxed mice; however, these differences are not observed in 20-week-old mice. The increased number of tartrate-resistant acid phosphatase (TRAP)-positive cells and serum levels of C-terminal telopeptides of type I collagen, a marker of bone resorption, in 6-week-old Pellino-1 cKO mice implied a connection between Pellino-1 and the osteoclast population. Enhanced TRAP activity and upregulation of osteoclast genes in BMMs from the cKO mice indicate that Pellino-1 deletion affects osteoclast differentiation, leading to decreased bone mass and heightened osteoclast activity. Thus, targeting Pellino-1 could be a potential gene therapy for managing and preventing osteoporosis.
Keyphrases
- bone loss
- high fat diet induced
- bone marrow
- transcription factor
- wild type
- gene expression
- type diabetes
- bone mineral density
- mesenchymal stem cells
- skeletal muscle
- small molecule
- risk assessment
- insulin resistance
- postmenopausal women
- genome wide
- drug delivery
- adipose tissue
- binding protein
- climate change
- heat stress
- cell cycle arrest