TY - JOUR
T1 - The role of the BH3-only protein Noxa in bone homeostasis
AU - Idrus, Erik
AU - Nakashima, Tomoki
AU - Wang, Ling
AU - Hayashi, Mikihito
AU - Okamoto, Kazuo
AU - Kodama, Tatsuhiko
AU - Tanaka, Nobuyuki
AU - Taniguchi, Tadatsugu
AU - Takayanagi, Hiroshi
N1 - Funding Information:
We thank T. Ando, Y. Kunisawa, K. Nishikawa, T. Negishi-Koga, A. Suematsu, M. Guerrini, and N. Komatsu for discussion and technical assistance. This work was supported in part by a scholarship from Japanese Government (Monbukagakusho); a Grant for ERATO, the Takayanagi Osteonetwork Project from the Japan Science and Technology Agency; Grant-in-Aid for Young Scientist A from the Japan Society for the Promotion of Science (JSPS); Grant-in-Aid for Challenging Exploratory Research from the JSPS; Grants for Global Center of Excellence Program from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT); and Grants from Tokyo Biochemical Research Foundation, Life Science Foundation of Japan, Takeda Science Foundation, Uehara Memorial Foundation, Nakatomi Foundation, Nagao Memorial Foundation, Kowa Life Science Foundation, Naito Foundation, Ichiro Kanehara Foundation, Senri Life Science Foundation and Astellas Foundation for Research on Metabolic Disorders.
PY - 2011/7/8
Y1 - 2011/7/8
N2 - Bone homeostasis is maintained by a dynamic balance between bone resorption by osteoclasts and bone formation by osteoblasts. Since excessive osteoclast activity is implicated in pathological bone resorption, understanding the mechanism underlying osteoclast differentiation, function and survival is of both scientific and clinical importance. Osteoclasts are monocyte/macrophage lineage cells with a short life span that undergo rapid apoptosis, the rate of which critically determines the level of bone resorption in vivo. However, the molecular basis of rapid osteoclast apoptosis remains obscure. Here we report the role of a BH3-only protein, Noxa (encoded by the Pmaip1 gene), in bone homeostasis using Noxa-deficient mice. Among the Bcl-2 family members, Noxa was selectively induced during osteoclastogenesis. Mice lacking Noxa exhibit a severe osteoporotic phenotype due to an increased number of osteoclasts. Noxa deficiency did not have any effect on the number of osteoclast precursor cells or the expression of osteoclast-specific genes, but led to a prolonged survival of osteoclasts. Furthermore, adenovirus-mediated Noxa overexpression remarkably reduced bone loss in a model of inflammation-induced bone destruction. This study reveals Noxa to be a crucial regulator of osteoclast apoptosis, and may provide a molecular basis for a new therapeutic approach to bone diseases.
AB - Bone homeostasis is maintained by a dynamic balance between bone resorption by osteoclasts and bone formation by osteoblasts. Since excessive osteoclast activity is implicated in pathological bone resorption, understanding the mechanism underlying osteoclast differentiation, function and survival is of both scientific and clinical importance. Osteoclasts are monocyte/macrophage lineage cells with a short life span that undergo rapid apoptosis, the rate of which critically determines the level of bone resorption in vivo. However, the molecular basis of rapid osteoclast apoptosis remains obscure. Here we report the role of a BH3-only protein, Noxa (encoded by the Pmaip1 gene), in bone homeostasis using Noxa-deficient mice. Among the Bcl-2 family members, Noxa was selectively induced during osteoclastogenesis. Mice lacking Noxa exhibit a severe osteoporotic phenotype due to an increased number of osteoclasts. Noxa deficiency did not have any effect on the number of osteoclast precursor cells or the expression of osteoclast-specific genes, but led to a prolonged survival of osteoclasts. Furthermore, adenovirus-mediated Noxa overexpression remarkably reduced bone loss in a model of inflammation-induced bone destruction. This study reveals Noxa to be a crucial regulator of osteoclast apoptosis, and may provide a molecular basis for a new therapeutic approach to bone diseases.
KW - Apoptosis
KW - Bcl-2 family proteins
KW - Noxa
KW - Osteoclast
UR - http://www.scopus.com/inward/record.url?scp=79960056564&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2011.06.040
DO - 10.1016/j.bbrc.2011.06.040
M3 - Article
C2 - 21689638
AN - SCOPUS:79960056564
SN - 0006-291X
VL - 410
SP - 620
EP - 625
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -