Treatment with intermittent PTH increases Wnt10b production by T cells in osteoporotic patients

被引:20
作者
D'Amelio, P. [1 ]
Sassi, F. [1 ]
Buondonno, I. [1 ]
Fornelli, G. [1 ]
Spertino, E. [1 ]
D'Amico, L. [2 ]
Marchetti, M. [1 ]
Lucchiari, M. [3 ]
Roato, I. [2 ]
Isaia, G. C. [1 ]
机构
[1] Univ Turin, Dept Med Sci, Gerontol Sect, I-10126 Turin, Italy
[2] Citta Salute & Sci Univ Hosp Torino Italy, CeRMS, Turin, Italy
[3] Citta Salute & Sci Univ Hosp Torino Italy, Clin Biochem Lab, Turin, Italy
关键词
Immune system; Osteoporosis; Primary hyperparathyroidism; PTH; Tcells; Wnt10b; HORMONE-RELATED PROTEIN; BONE ANABOLIC ACTIVITY; PARATHYROID-HORMONE; PRIMARY HYPERPARATHYROIDISM; POSTMENOPAUSAL WOMEN; MINERAL DENSITY; STRUT ANALYSIS; SCLEROSTIN; OSTEOCYTES; HISTOMORPHOMETRY;
D O I
10.1007/s00198-015-3189-8
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We evaluated the effect of parathyroid hormone (PTH) on Wnt10b production by immune system cells in humans. We showed that bone anabolic effect of intermittent PTH treatment may be amplified by T cells through increased production of Wnt10b. Chronic increase in PTH as in primary hyperparathyroidism does not increase Wnt10b expression. Introduction The aim of this study is to assess the effect of PTH on Wnt10b production by immune system cells in humans. We assessed both the effect of intermittent PTH administration (iPTH) and of chronic PTH hypersecretion in primary hyperparathyroidism (PHP). Methods Eighty-two women affected by post-menopausal osteoporosis were randomly assigned to treatment with calcium and vitamin D alone (22) or plus 1-84 PTH (42), or intravenous ibandronate (18). Wnt10b production by unfractioned blood nucleated cells and by T, B cells and monocytes was assessed by real-time RT-PCR and ELISA at baseline, 3, 6, 12 and 18 months of treatment. The effect of chronic elevation of PTH was evaluated in 20 patients affected by PHP at diagnosis and after surgical removal of parathyroid adenoma. WNT10b from both osteoporotic and PHP patients was compared to healthy subjects matched for age and sex. Results iPTH increases Wnt10b production by T cells, whereas PHP does not. After surgical restoration of normal parathyroid function, WNT10b decreases, although it is still comparable with healthy subjects' level. Thus, chronic elevation of PTH does not significantly increase WNT10b production as respect to control. Conclusions This is the first work showing the effect of both intermittent and chronic PTH increase on Wnt10b production by immune system cells. We suggest that, in humans, T cells amplified the anabolic effect of PTH on bone, by increasing Wnt10b production, which stimulates osteoblast activity.
引用
收藏
页码:2785 / 2791
页数:7
相关论文
共 26 条
[1]   Decreased serum sclerostin levels in patients with primary hyperparathyroidism: a cross-sectional and a longitudinal study [J].
Ardawi, M. -S. M. ;
Al-Sibiany, A. M. ;
Bakhsh, T. M. ;
Rouzi, A. A. ;
Qari, M. H. .
OSTEOPOROSIS INTERNATIONAL, 2012, 23 (06) :1789-1797
[2]   Silencing of parathyroid hormone (PTH) receptor 1 in T cells blunts the bone anabolic activity of PTH [J].
Bedi, Brahmchetna ;
Li, Jau-Yi ;
Tawfeek, Hesham ;
Baek, Ki-Hyun ;
Adams, Jonathan ;
Vangara, Sameera S. ;
Chang, Ming-Kang ;
Kneissel, Michaela ;
Weitzmanna, M. Neale ;
Pacifici, Roberto .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (12) :E725-E733
[3]   Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: A novel mechanism for hormonal control of osteoblastogenesis [J].
Bellido, T ;
Ali, AA ;
Gubrij, I ;
Plotkin, LI ;
Fu, Q ;
O'Brien, CA ;
Manolagas, SC ;
Jilka, RL .
ENDOCRINOLOGY, 2005, 146 (11) :4577-4583
[4]   Increases in BMD correlate with improvements in bone microarchitecture with Teriparatide treatment in postmenopausal women with osteoporosis [J].
Chen, Peiqi ;
Miller, Paul D. ;
Recker, Robert ;
Resch, Heinrich ;
Rana, Asad ;
Pavo, Imre ;
Sipos, Adrien A. .
JOURNAL OF BONE AND MINERAL RESEARCH, 2007, 22 (08) :1173-1180
[5]   Targeted deletion of Sost distal enhancer increases bone formation and bone mass [J].
Collette, Nicole M. ;
Genetos, Damian C. ;
Economides, Aris N. ;
Xie, LiQin ;
Shahnazari, Mohammad ;
Yao, Wei ;
Lane, Nancy E. ;
Harland, Richard M. ;
Loots, Gabriela G. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (35) :14092-14097
[6]   Effects of Parathyroid Hormone Treatment on Circulating Sclerostin Levels in Postmenopausal Women [J].
Drake, Matthew T. ;
Srinivasan, Bhuma ;
Moedder, Ulrike I. ;
Peterson, James M. ;
McCready, Louise K. ;
Riggs, B. Lawrence ;
Dwyer, Denise ;
Stolina, Marina ;
Kostenuik, Paul ;
Khosla, Sundeep .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2010, 95 (11) :5056-5062
[7]   Nuclear localization of type I parathyroid hormone/parathyroid hormone-related protein receptors in deer antler osteoclasts:: Evidence for parathyroid hormone-related protein and receptor activator of NF-κB-dependent effects on osteoclast formation in regenerating mammalian bone [J].
Faucheux, C ;
Horton, MA ;
Price, JS .
JOURNAL OF BONE AND MINERAL RESEARCH, 2002, 17 (03) :455-464
[8]   Cellular mechanism through which parathyroid hormone-related protein induces proliferation in arterial smooth muscle cells -: Definition of an arterial smooth muscle PTHrP/p27kip1 pathway [J].
Fiaschi-Taesch, Nathalie ;
Sicari, Brian M. ;
Ubriani, Kiran ;
Bigatel, Todd ;
Takane, Karen K. ;
Cozar-Castellano, Irene ;
Bisello, Alessandro ;
Law, Brian ;
Stewart, Andrew F. .
CIRCULATION RESEARCH, 2006, 99 (09) :933-942
[9]   International Union of Basic and Clinical Pharmacology. XCIII. The Parathyroid Hormone Receptors-Family B G Protein-Coupled Receptors [J].
Gardella, Thomas J. ;
Vilardaga, Jean-Pierre .
PHARMACOLOGICAL REVIEWS, 2015, 67 (02) :310-337
[10]   Hypoxia Decreases Sclerostin Expression and Increases Wnt Signaling in Osteoblasts [J].
Genetos, Damian C. ;
Toupadakis, Chrisoula A. ;
Raheja, Leah F. ;
Wong, Alice ;
Papanicolaou, Savvas E. ;
Fyhrie, David P. ;
Loots, Gabriela G. ;
Yellowley, Clare E. .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2010, 110 (02) :457-467