Anti-apoptotic Bcl-2 family member Mcl-1 regulates cell viability and bone-resorbing activity of osteoclasts.

Abstract

Myeloid cell leukemia sequence 1 (Mcl-1) is an anti-apoptotic Bcl-2 family protein and an immediate early gene expressed during myeloid leukemia cell line differentiation. We analyzed the expression and function of Mcl-1 in osteoclasts. Mcl-1 protein exhibited a short half-life in osteoclasts caused by its degradation in the ubiquitin-proteasome system. Mcl-1 had no effect on osteoclast differentiation, but its overexpression prolonged osteoclast survival and suppressed the bone-resorbing activity of these cells, as determined by pit formation assay. Conversely, Mcl-1 depletion suppressed osteoclast survival and increased bone resorption. This negative role for Mcl-1 on the bone-resorptive activities of osteoclasts may be caused by the increase in adenosine triphosphate/adenosine diphosphate ratio. Finally, we showed that the local deletion of Mcl-1 by the injection of the Cre adenovirus into the calvaria of Mcl1(fl/fl) mice significantly affected GST-RANKL-induced bone resorption in vivo. These results demonstrated that Mcl-1 positively regulates cell viability and negatively regulates the bone-resorbing activity of osteoclasts both in vitro and in vivo.

• Authors: Hironari Masuda, Jun Hirose, Yasunori Omata, Naoto Tokuyama, Tetsuro Yasui, Yuho Kadono, Tsuyoshi Miyazaki, Sakae Tanaka
• Journal: Bone (Bone) Vol. 58 Pg. 1-10 (Jan 2014) ISSN: 1873-2763 [Electronic] United States
• PMID: 24096094 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013.

Chemical References

• Myeloid Cell Leukemia Sequence 1 Protein
• Ubiquitin
• Adenosine Triphosphate
• Extracellular Signal-Regulated MAP Kinases
• Proteasome Endopeptidase Complex

Topics

• Adenosine Triphosphate (biosynthesis)
• Animals
• Apoptosis
• Bone Resorption (metabolism, pathology)
• Cell Differentiation
• Cell Survival
• Cytoskeleton (metabolism)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mitochondria (metabolism)
• Myeloid Cell Leukemia Sequence 1 Protein (metabolism)
• Osteoclasts (enzymology, metabolism, pathology)
• Proteasome Endopeptidase Complex (metabolism)
• Proteolysis
• Ubiquitin (metabolism)