Age-Related Decrease in Pellino-1 Expression Contributes to Osteoclast-Mediated Bone Loss.

Autor: Yoon DS; Department of Biomedical Science, Hwasung Medi-Science University, Hwasung, Gyeonggi-Do, 18274, South Korea.; Stem Cell and Aging Laboratory, Institute of HSMU Medi-Science, Hwasung Medi-Science University, Hwaseong, Gyeonggi-Do, 18274, South Korea., Oh SE; Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, 03722, South Korea.; Department of Orthopaedic Surgery, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, 03722, South Korea., Lee KM; Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, 03722, South Korea.; Department of Orthopaedic Surgery, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, 03722, South Korea., Jung S; Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, 03722, South Korea.; Department of Orthopaedic Surgery, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, 03722, South Korea., Ko EA; Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, 03722, South Korea., Kim TG; Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, 03722, South Korea.; Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, 03722, South Korea., Park KH; Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, 03722, South Korea., Lee JW; Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, 03722, South Korea.; Department of Orthopaedic Surgery, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, 03722, South Korea.
Jazyk: angličtina
Zdroj: Advanced biology [Adv Biol (Weinh)] 2024 Jul; Vol. 8 (7), pp. e2400210. Date of Electronic Publication: 2024 May 07.
DOI: 10.1002/adbi.202400210
Abstrakt: 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.
(© 2024 The Authors. Advanced Biology published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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