TY - JOUR
T1 - PGC1β Organizes the Osteoclast Cytoskeleton by Mitochondrial Biogenesis and Activation
AU - Zhang, Yan
AU - Rohatgi, Nidhi
AU - Veis, Deborah J.
AU - Schilling, Joel
AU - Teitelbaum, Steven L.
AU - Zou, Wei
N1 - Publisher Copyright:
© 2018 American Society for Bone and Mineral Research
PY - 2018/6
Y1 - 2018/6
N2 - Osteoclasts are mitochondria-rich cells, but the role of these energy-producing organelles in bone resorption is poorly defined. To this end, we conditionally deleted the mitochondria-inducing co-activator, PGC1β, in myeloid lineage cells to generate PGC1βLysM mice. In contrast to previous reports, PGC1β-deficient macrophages differentiate normally into osteoclasts albeit with impaired resorptive function due to cytoskeletal disorganization. Consequently, bone mass of PGC1βLysM mice is double that of wild type. Mitochondrial biogenesis and function are diminished in PGC1βLysM osteoclasts. All abnormalities are normalized by PGC1β transduction. Furthermore, OXPHOS inhibitors reproduce the phenotype of PGC1β deletion. PGC1β's organization of the osteoclast cytoskeleton is mediated by expression of GIT1, which also promotes mitochondrial biogenesis. Thus, osteoclast mitochondria regulate the cell's resorptive activity by promoting cytoskeletal organization.
AB - Osteoclasts are mitochondria-rich cells, but the role of these energy-producing organelles in bone resorption is poorly defined. To this end, we conditionally deleted the mitochondria-inducing co-activator, PGC1β, in myeloid lineage cells to generate PGC1βLysM mice. In contrast to previous reports, PGC1β-deficient macrophages differentiate normally into osteoclasts albeit with impaired resorptive function due to cytoskeletal disorganization. Consequently, bone mass of PGC1βLysM mice is double that of wild type. Mitochondrial biogenesis and function are diminished in PGC1βLysM osteoclasts. All abnormalities are normalized by PGC1β transduction. Furthermore, OXPHOS inhibitors reproduce the phenotype of PGC1β deletion. PGC1β's organization of the osteoclast cytoskeleton is mediated by expression of GIT1, which also promotes mitochondrial biogenesis. Thus, osteoclast mitochondria regulate the cell's resorptive activity by promoting cytoskeletal organization.
KW - CYTOSKELETON
KW - MITOCHONDRIAL BIOGENESIS
KW - OSTEOCLASTS
KW - PGC1β
UR - http://www.scopus.com/inward/record.url?scp=85047059726&partnerID=8YFLogxK
U2 - 10.1002/jbmr.3398
DO - 10.1002/jbmr.3398
M3 - Article
C2 - 29521005
AN - SCOPUS:85047059726
SN - 0884-0431
VL - 33
SP - 1114
EP - 1125
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
IS - 6
ER -