Elucidation of a novel regulatory mechanism of bone metabolism by cellular senescence regulators and its therapeutic application
Description: We analyzed the role of basic HLH-type transcription factors involved in cellular senescence in bone metabolism and bone aging. bHLH-1 knockout (KO) mice showed increased bone mass and bone formation in femurs, and osteoblasts showed increased proliferation and differentiation of progenitor cells, and increased number of osteocytes. On the other hand, autophagy in osteoblasts was increased whereas apoptosis in osteoblasts and osteocytes was decreased. The bone mass of bHLH-1 KO mice was higher than that of wild type (WT) mice even in old age, and the bone loss due to aging was also reduced. Furthermore, the expression of senescent marker genes was decreased in osteoblasts and osteocytes of bHLH-1 KO mice, suggesting that bHLH-1 may be involved in the accumulation of senescent cells and age-related bone loss.
Amount: ¥4,420,000
Funding type: research
Funder scheme: Grant-in-Aid for Scientific Research (C)
Start date: 2018-04-01
End date: 2021-03-31
Investigator: Akiko Kukita
Institution: Saga University
Topic: Bone Metabolism and Diseases
Subfield: Molecular Biology
Domain: Life Sciences
Funded outputs count: 5
Funder award ID: 18K09034
OpenAlex ID: G6445369256