ATP6v0d2 deficiency increases bone mass, but does not influence ovariectomy-induced bone loss.
Bone homeostasis is maintained through the balanced action of bone-forming osteoblasts and bone-resorbing osteoclasts. Under pathological conditions or with age, excessive bone loss is often observed due to increased bone resorption. Since osteoclasts are the primary cells in the body that can resorb bone, molecular understanding of osteoclast fate has important clinical implications. Over the past 20 years, many molecular players that govern osteoclast differentiation during normal development have been identified. However, whether the same molecules regulate bone loss occurring under pathological conditions remains largely unknown. We report here that although ATP6v0d2-deficient (ATP6v0d2 KO) mice exhibit an osteopetrotic phenotype due to inefficient osteoclast maturation, this deficiency fails to protect mice from ovariectomy (OVX)-induced bone loss, a model for post-menopause-associated osteoporosis. Moreover, we show that an OVX-induced increase in the number of colony forming unit-granulocyte/macrophage (CFU-GM) in bone marrow cells and subsequent osteoclast formation in vitro was not affected in the absence of ATP6v0d2. However, even after OVX, formation of large osteoclasts (>100 μm in diameter) with actin rings was still reduced in the absence of ATP6v0d2. Taken together, these findings suggest that the critical role of ATP6v0d2 may be limited to the control of bone homeostasis under normal development, and that OVX-induced bone loss is likely to be governed mostly by the increase in osteoclast precursors rather than increased efficiency of osteoclast maturation.
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Taesoo
T
Kim
Hyunil
H
Ha
Nacksung
N
Kim
Eui-Soon
ES
Park
Jaerang
J
Rho
Eun Cheol
EC
Kim
Joseph
J
Lorenzo
Yongwon
Y
Choi
Seoung Hoon
SH
Lee
D000818:Animals; D015519:Bone Density; D001842:Bone and Bones / Q000166:cytology*; D002454:Cell Differentiation; D051379:Mice; D018345:Mice, Knockout; D010010:Osteoclasts / Q000166:cytology; D010024:Osteoporosis / Q000378:metabolism / Q000473:pathology; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics / Q000502:physiology*
C542312:Atp6v0d2 protein, mouse; D025262:Vacuolar Proton-Translocating ATPases