- Email: [email protected]
Microtubule dynamics affect bone mass by regulating both osteoblast and osteoclast function — Stathmin deficiency produces an osteopenic phenotype in mice
S364
Abstracts / Bone 47 (2010) S361–S375
OP7 Contribution of the Myostatin gene polymorphisms to normal variation in lean mass and fat mass in Chinese male offspring nuclear families Hua Yue, Jin-Wei He, Zhen-Lin Zhang, Hao Zhang, Chun Wang, Yao-Hua Ke, Wen-Zhen Fu, Wei-Wei Hu, Jie-Mei Gu, Yun-Qiu Hu, Miao Li, Yu-Juan Liu The Department of Osteoporosis, Bone Metabolic Disease & Genetics Research Unit, Shanghai Jiaotong University Affiliated the Sixth People's Hospital, Shanghai, China Objective: To date, no study has been performed on the genetic association of Myostatin gene polymorphisms and obesity-related traits variations in the Chinese male nuclear families. Our study is aimed to investigate the association of Myostatin gene polymorphisms and peak bone mineral density (peak BMD), lean mass (LM) and fat mass (FM) variations in Chinese men. Methods: We recruited 400 male nuclear families composed of 1215 individuals with at least one male child. The studied SNPs are tag-SNPs, which were selected from International HapMap Project and genotyped by TaqMan. BMD, fat mass and lean mass were measured by DXA on a GE-LUNAR prodigy (USA). Results: All 3 polymorphisms met the expectations of Hardy– Weinberg equilibrium. Using QTDT, we failed to find within-family association between any polymorphism and haplotype with peak BMD in male nuclear families. Significant within-family association was detected between fat mass variation and rs3791783 at trunk (p < 0.001) and permutation 1000 tests were in agreement with the finding (p < 0.001). Moreover, for within-family association, significant associations were found between haplotype AGG, AAA and TGG and the trunk fat mass, respectively (all p < 0.001). Conclusions: These results suggested, for the first time, the genetic polymorphisms in Myostatin have an effect on normal variation in obesity-related phenotypes.
as demonstrated by decreased osteoblast number and osteoblast surface, attenuated ALP activity in primary calvarial and bone marrow osteoblastic cells, and decreased expression of osteoblast maturation genes including BMP2, Runx2 and Col1a1. We also found that inactivation of the stathmin gene promoted osteoclast formation in bone tissue, as demonstrated by increased number and surface area of Trap positive osteoclast cells, and enhanced levels of osteoclast marker genes including RNAK, RNAKL ATP6, CTSK with decreased OPG levels. Next, we examined the effects of overexpression of stathmin on osteoblast and osteoclast formation in cell lines and primary bone cells. We found that overexpression of stathmin in MC3T3-E1 cells increased ALP activity, stimulated bone nodule formation, and induced BMP2, Col1a1 and OCN expression. In contrast, overexpression of stathmin in bone marrow cells inhibited osteoclast formation with a reduced RANKL/OPG ratio. Lastly, immunofluorescent studies showed disruption of microtubule filament structure in these stathmin-overexpressed bone cells compared with control cells. Collectively, these findings strongly support the conclusion that stathmin, which regulates microtubule dynamics, plays an essential role in maintenance of postnatal bone mass by regulating differentiation of osteoblasts and osteoclast in bone.
doi:10.1016/j.bone.2010.09.097
OP9 The effect of hypoxia on differentiation from myeloid-like cells to osteoclasts in mouse Xiaolan Jin General Hospital of Chengdu Military Region, Chengdu, China Abstract content written in Chinese only.
doi:10.1016/j.bone.2010.09.096 doi:10.1016/j.bone.2010.09.098 OP8 Microtubule dynamics affect bone mass by regulating both osteoblast and osteoclast function — Stathmin deficiency produces an osteopenic phenotype in mice Hongbin Liu1, Rongrong Zhang1, Seon-yle Ko2, Christopher Papasian1, Hong-wen Deng1, Ming Zhao1 1 Univeristy of Missouri-Kansas City, Kansas City, MO, USA 2 Dankook University, Seoul, Republic of Korea Cytoskeleton microtubules regulate various cell signaling pathways that are involved in bone cell function. We recently reported that inhibition of microtubule assembly by microtubule-targeting drugs stimulates osteoblast differentiation and bone formation (Zhao et al, MCB, 2009). To further elucidate the mechanisms by which microtubules function in bone, we used a knockout mouse model to investigate the physiological role of stathmin, an endogenous protein that inhibits microtubule assembly, in bone. Global stathmin knockout mice, in which exons II and III of the stathmin gene were removed, were maintained in a heterozygous state on a C57BL/6 background. The bone phenotype of homozygous mutant mice and their wild-type littermates were examined at two months of age. Examination by mCT and histology revealed a substantial reduction of bone mass in stathmin-deficient mice compared with control mice, as indicated by decreased bone mineral density, trabecular bone volume, trabecular thickness, trabecular number, and increased trabecular separation of long bones. Further examination of these bone tissues showed that osteoblast function was markedly inhibited by deletion of stathmin,
OP10 Association between abdominal aortic calcification and osteoporosis in postmenopausal women in Beijing Ningyi Cui, Weibo Xia, Yan Jiang, Qiang Lin, Wei Yu, Mei Li, Ou Wang, Min Nie, Yue Sun, Shuli He, Jing Sun, Xiaoping Xing, Xunwu Meng, Yingying Hu, Huaicheng Liu, Xueying Zhou Department of Endocrinology, Key Laboratory of Endocrinology Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China
Objective: There is growing evidence for the association between osteoporosis and vascular calcification, which is related to cardiovascular disease. The objective of this study was to investigate the correlation between abdominal aortic calcification (AAC) and osteoporosis in postmenopausal women in Beijing. We evaluated bone mineral density (BMD) of different sites, osteoporotic vertebra fractures and AAC — a surrogate marker of atherosclerosis. Methods: A total of 1606 generally healthy postmenopausal women were randomly recruited based in communities in Beijing. Demographic information, osteoporosis risk factors and cardiovascular risk factors were obtained through standard questionnaires. BMD of femoral neck and lumbar spine (L2–4) was measured with dual energy X-ray absorptiometry. Vertebra fractures were ascertained by lateral radiographs, and AAC on lateral radiographs was assessed by AAC-24 score system established previously. Logistic regression models were applied to evaluate the association between AAC, BMD, and vertebral fractures. Results: (1)
Abstracts / Bone 47 (2010) S361–S375
OP7 Contribution of the Myostatin gene polymorphisms to normal variation in lean mass and fat mass in Chinese male offspring nuclear families Hua Yue, Jin-Wei He, Zhen-Lin Zhang, Hao Zhang, Chun Wang, Yao-Hua Ke, Wen-Zhen Fu, Wei-Wei Hu, Jie-Mei Gu, Yun-Qiu Hu, Miao Li, Yu-Juan Liu The Department of Osteoporosis, Bone Metabolic Disease & Genetics Research Unit, Shanghai Jiaotong University Affiliated the Sixth People's Hospital, Shanghai, China Objective: To date, no study has been performed on the genetic association of Myostatin gene polymorphisms and obesity-related traits variations in the Chinese male nuclear families. Our study is aimed to investigate the association of Myostatin gene polymorphisms and peak bone mineral density (peak BMD), lean mass (LM) and fat mass (FM) variations in Chinese men. Methods: We recruited 400 male nuclear families composed of 1215 individuals with at least one male child. The studied SNPs are tag-SNPs, which were selected from International HapMap Project and genotyped by TaqMan. BMD, fat mass and lean mass were measured by DXA on a GE-LUNAR prodigy (USA). Results: All 3 polymorphisms met the expectations of Hardy– Weinberg equilibrium. Using QTDT, we failed to find within-family association between any polymorphism and haplotype with peak BMD in male nuclear families. Significant within-family association was detected between fat mass variation and rs3791783 at trunk (p < 0.001) and permutation 1000 tests were in agreement with the finding (p < 0.001). Moreover, for within-family association, significant associations were found between haplotype AGG, AAA and TGG and the trunk fat mass, respectively (all p < 0.001). Conclusions: These results suggested, for the first time, the genetic polymorphisms in Myostatin have an effect on normal variation in obesity-related phenotypes.
as demonstrated by decreased osteoblast number and osteoblast surface, attenuated ALP activity in primary calvarial and bone marrow osteoblastic cells, and decreased expression of osteoblast maturation genes including BMP2, Runx2 and Col1a1. We also found that inactivation of the stathmin gene promoted osteoclast formation in bone tissue, as demonstrated by increased number and surface area of Trap positive osteoclast cells, and enhanced levels of osteoclast marker genes including RNAK, RNAKL ATP6, CTSK with decreased OPG levels. Next, we examined the effects of overexpression of stathmin on osteoblast and osteoclast formation in cell lines and primary bone cells. We found that overexpression of stathmin in MC3T3-E1 cells increased ALP activity, stimulated bone nodule formation, and induced BMP2, Col1a1 and OCN expression. In contrast, overexpression of stathmin in bone marrow cells inhibited osteoclast formation with a reduced RANKL/OPG ratio. Lastly, immunofluorescent studies showed disruption of microtubule filament structure in these stathmin-overexpressed bone cells compared with control cells. Collectively, these findings strongly support the conclusion that stathmin, which regulates microtubule dynamics, plays an essential role in maintenance of postnatal bone mass by regulating differentiation of osteoblasts and osteoclast in bone.
doi:10.1016/j.bone.2010.09.097
OP9 The effect of hypoxia on differentiation from myeloid-like cells to osteoclasts in mouse Xiaolan Jin General Hospital of Chengdu Military Region, Chengdu, China Abstract content written in Chinese only.
doi:10.1016/j.bone.2010.09.096 doi:10.1016/j.bone.2010.09.098 OP8 Microtubule dynamics affect bone mass by regulating both osteoblast and osteoclast function — Stathmin deficiency produces an osteopenic phenotype in mice Hongbin Liu1, Rongrong Zhang1, Seon-yle Ko2, Christopher Papasian1, Hong-wen Deng1, Ming Zhao1 1 Univeristy of Missouri-Kansas City, Kansas City, MO, USA 2 Dankook University, Seoul, Republic of Korea Cytoskeleton microtubules regulate various cell signaling pathways that are involved in bone cell function. We recently reported that inhibition of microtubule assembly by microtubule-targeting drugs stimulates osteoblast differentiation and bone formation (Zhao et al, MCB, 2009). To further elucidate the mechanisms by which microtubules function in bone, we used a knockout mouse model to investigate the physiological role of stathmin, an endogenous protein that inhibits microtubule assembly, in bone. Global stathmin knockout mice, in which exons II and III of the stathmin gene were removed, were maintained in a heterozygous state on a C57BL/6 background. The bone phenotype of homozygous mutant mice and their wild-type littermates were examined at two months of age. Examination by mCT and histology revealed a substantial reduction of bone mass in stathmin-deficient mice compared with control mice, as indicated by decreased bone mineral density, trabecular bone volume, trabecular thickness, trabecular number, and increased trabecular separation of long bones. Further examination of these bone tissues showed that osteoblast function was markedly inhibited by deletion of stathmin,
OP10 Association between abdominal aortic calcification and osteoporosis in postmenopausal women in Beijing Ningyi Cui, Weibo Xia, Yan Jiang, Qiang Lin, Wei Yu, Mei Li, Ou Wang, Min Nie, Yue Sun, Shuli He, Jing Sun, Xiaoping Xing, Xunwu Meng, Yingying Hu, Huaicheng Liu, Xueying Zhou Department of Endocrinology, Key Laboratory of Endocrinology Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China
Objective: There is growing evidence for the association between osteoporosis and vascular calcification, which is related to cardiovascular disease. The objective of this study was to investigate the correlation between abdominal aortic calcification (AAC) and osteoporosis in postmenopausal women in Beijing. We evaluated bone mineral density (BMD) of different sites, osteoporotic vertebra fractures and AAC — a surrogate marker of atherosclerosis. Methods: A total of 1606 generally healthy postmenopausal women were randomly recruited based in communities in Beijing. Demographic information, osteoporosis risk factors and cardiovascular risk factors were obtained through standard questionnaires. BMD of femoral neck and lumbar spine (L2–4) was measured with dual energy X-ray absorptiometry. Vertebra fractures were ascertained by lateral radiographs, and AAC on lateral radiographs was assessed by AAC-24 score system established previously. Logistic regression models were applied to evaluate the association between AAC, BMD, and vertebral fractures. Results: (1)