Changes in serum runt-related transcription factor 2 levels after a 6-month treatment with recombinant human parathyroid hormone in patients with osteoporosis

被引:6
作者
Zhu, W. [1 ,2 ]
Yang, M. L. [3 ]
Yang, G. Y. [3 ]
Boden, G. [4 ,5 ]
Li, L. [1 ,2 ]
机构
[1] Chongqing Med Univ, Dept Clin Biochem, Coll Lab Med, Chongqing, Peoples R China
[2] Chongqing Med Univ, Key Lab Lab Med Diagnost, Coll Lab Med, Minist Educ, Chongqing, Peoples R China
[3] Chongqing Med Univ, Dept Endocrinol, Affiliated Hosp 2, Chongqing, Peoples R China
[4] Temple Univ, Sch Med, Div Endocrinol Diabet Metab, Philadelphia, PA 19122 USA
[5] Temple Univ, Sch Med, Clin Res Ctr, Philadelphia, PA 19122 USA
基金
中国国家自然科学基金;
关键词
Bone mineral density; matrix metalloproteinase 13; osteoporosis; recombinant human parathyroid hormone; Runt-related transcription factor 2; BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; OSTEOBLAST DIFFERENTIATION; ESTABLISHED OSTEOPOROSIS; COLLAGENASE; CBFA1; EXPRESSION; TERIPARATIDE; INDUCTION; ACTIVATOR;
D O I
10.3275/8110
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
Background: The mechanisms regulating the anabolic response of the skeleton for recombinant human PTH (1-34) [rhPTH (1-34)] administration has not been fully elucidated. Aim: The aim of this study was to evaluate the effect of rhPTH (1-34) on serum levels of runt-related transcription factor 2 (Runx2) in women with osteoporosis. Methods: Sixty postmenopausal women with osteoporosis (EO group) and 45 control subjects (NC group) were enrolled in this study. The EO group received daily injection of 20 mu g rhPTH (1-34) plus oral 500 mg elemental calcium and 400 IU vitamin D3 for 6 months. Runx2 and Matrix metalloproteinase 13 (MMP-13) were measured with commercially available enzyme-linked immunosorbent assay kits. Bone mineral density (BMD) was also measured before and 6 months after rhPTH (1-34) treatment. Results: Serum total Ca2+, phosphate, and bone-specific alkaline phosphatase were significantly increased (p<0.05 or p<0.01), and the lumbar spine BMD (LS-BMD) was also increased by 4% in patients with osteoporosis after treatment with rhPTH (1-34) (p<0.05). On the contrary, serum Runx2 and MMP-13 were significantly decreased at post treatment (13.1% and 36.6%, respectively, p<0.05 and p<0.01). At baseline, serum Runx2 positively correlated with MMP-13 (r=0.74, p<0.01), the correction remained after adjusting for age and body mass index. Conclusion: The daily injection of rhPTH (1-34) was able to stimulate bone formation. The therapy of 20 mu g rhPTH (1-34) for 6 months resulted in decrease of serum Runx2 and MMP-13. These changes might reflect the increase of active osteoblasts and the better bone homeostasis. (J. Endocrinol. Invest. 35: 602-606, 2012) (C) 2012, Editrice Kurtis
引用
收藏
页码:602 / 606
页数:5
相关论文
共 39 条
[1]
Albala C, 1996, INT J OBESITY, V20, P1027
[2]
Acute changes in serum osteoprotegerin and receptor activator for nuclear factor-κB ligand levels in women with established osteoporosis treated with teriparatide [J].
Anastasilakis, Athanasios D. ;
Goulis, Dimirtios G. ;
Polyzos, Stergios A. ;
Gerou, Spiridon ;
Pavlidou, Vasiliki ;
Koukoulis, George ;
Avramidis, Avraam .
EUROPEAN JOURNAL OF ENDOCRINOLOGY, 2008, 158 (03) :411-415
[3]
Proteasomal degradation of Runx2 shortens parathyroid hormone-induced anti-apoptotic signaling in osteoblasts - A putative explanation for why intermittent administration is needed for bone anabolism [J].
Bellido, T ;
Ali, AA ;
Plotkin, LI ;
Fu, Q ;
Gubrij, I ;
Roberson, PK ;
Weinstein, RS ;
O'Brien, CA ;
Manolagas, SC ;
Jilka, RL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (50) :50259-50272
[4]
EVIDENCE THAT INTERMITTENT TREATMENT WITH PARATHYROID-HORMONE INCREASES BONE-FORMATION IN ADULT-RATS BY ACTIVATION OF BONE LINING CELLS [J].
DOBNIG, H ;
TURNER, RT .
ENDOCRINOLOGY, 1995, 136 (08) :3632-3638
[5]
Osf2/Cbfa1: A transcriptional activator of osteoblast differentiation [J].
Ducy, P ;
Zhang, R ;
Geoffroy, V ;
Ridall, AL ;
Karsenty, G .
CELL, 1997, 89 (05) :747-754
[6]
A Cbfa1-dependent genetic pathway controls bone formation beyond embryonic development [J].
Ducy, P ;
Starbuck, M ;
Priemel, M ;
Shen, JH ;
Pinero, G ;
Geoffroy, V ;
Amling, M ;
Karsenty, G .
GENES & DEVELOPMENT, 1999, 13 (08) :1025-1036
[7]
TOWARD A MOLECULAR UNDERSTANDING OF SKELETAL DEVELOPMENT [J].
ERLEBACHER, A ;
FILVAROFF, EH ;
GITELMAN, SE ;
DERYNCK, R .
CELL, 1995, 80 (03) :371-378
[8]
Regulation of the osteoblast-specific transcription factor, runx2: Responsiveness to multiple signal transduction pathways [J].
Franceschi, RT ;
Xiao, GZ .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2003, 88 (03) :446-454
[9]
Interleukin-6 and its soluble receptor cause a marked induction of collagenase 3 expression in rat osteoblast cultures [J].
Franchimont, N ;
Rydziel, S ;
Delany, AM ;
Canalis, E .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (18) :12144-12150
[10]
AP-1 and Cbfa/runt physically interact and regulate parathyroid hormone-dependent MMP13 expression in osteoblasts through a new osteoblast-specific element 2/AP-1 composite element [J].
Hess, J ;
Porte, D ;
Munz, C ;
Angel, P .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (23) :20029-20038