蛋白酶体抑制剂硼替佐米对新骨形成的刺激作用：对骨髓瘤骨病的影响
Stimulation of new bone formation by the proteasome inhibitor, bortezomib: implications for myeloma bone disease.
作者信息
Oyajobi Babatunde O, Garrett I Ross, Gupta Anjana, Flores Alda, Esparza Javier, Muñoz Steve, Zhao Ming, Mundy Gregory R
机构信息
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
出版信息
Br J Haematol. 2007 Nov;139(3):434-8. doi: 10.1111/j.1365-2141.2007.06829.x.
Abstract
Impaired bone formation contributes to the lack of bone healing in multiple myeloma and there is a need for agents with bone anabolic properties to reverse the bone deficit in patients. Bortezomib, a proteasome inhibitor with antitumour efficacy in myeloma patients, enhanced new bone formation in mouse calvarial cultures; this effect was blocked by dickkopf 1(Dkk1), an antagonist of Wnt signalling implicated in myeloma bone disease. Bortezomib inhibited Dkk1 expression in calvariae and bone marrow-derived stromal cells, suggesting a novel mechanism by which bortezomib exerts its effects in bone. Clinical trials in patients with myeloma bone disease are needed to validate these results.
摘要
骨形成受损导致多发性骨髓瘤患者骨愈合不足，因此需要具有骨合成代谢特性的药物来逆转患者的骨缺损。硼替佐米是一种对骨髓瘤患者具有抗肿瘤疗效的蛋白酶体抑制剂，可增强小鼠颅骨培养物中的新骨形成；这种作用被Dickkopf 1（Dkk1）阻断，Dkk1是一种参与骨髓瘤骨病的Wnt信号拮抗剂。硼替佐米抑制颅骨和骨髓来源的基质细胞中Dkk1的表达，提示硼替佐米在骨中发挥作用的一种新机制。需要对骨髓瘤骨病患者进行临床试验以验证这些结果。
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本文引用的文献
1
Bortezomib reduces serum dickkopf-1 and receptor activator of nuclear factor-kappaB ligand concentrations and normalises indices of bone remodelling in patients with relapsed multiple myeloma.
Br J Haematol. 2006 Dec;135(5):688-92. doi: 10.1111/j.1365-2141.2006.06356.x.
2
Bortezomib: proteasome inhibition as an effective anticancer therapy.
Annu Rev Med. 2006;57:33-47. doi: 10.1146/annurev.med.57.042905.122625.
3
Response to bortezomib is associated to osteoblastic activation in patients with multiple myeloma.
Br J Haematol. 2005 Oct;131(1):71-3. doi: 10.1111/j.1365-2141.2005.05733.x.
4
Essential role of beta-catenin in postnatal bone acquisition.
J Biol Chem. 2005 Jun 3;280(22):21162-8. doi: 10.1074/jbc.M501900200. Epub 2005 Mar 31.
5
The Wnt antagonist DICKKOPF-1 gene is a downstream target of beta-catenin/TCF and is downregulated in human colon cancer.
Oncogene. 2005 Feb 3;24(6):1098-103. doi: 10.1038/sj.onc.1208303.
6
The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma.
N Engl J Med. 2003 Dec 25;349(26):2483-94. doi: 10.1056/NEJMoa030847.
7
A role for Wnt/beta-catenin signaling in lens epithelial differentiation.
Dev Biol. 2003 Jul 1;259(1):48-61. doi: 10.1016/s0012-1606(03)00179-9.
8
Selective inhibitors of the osteoblast proteasome stimulate bone formation in vivo and in vitro.
J Clin Invest. 2003 Jun;111(11):1771-82. doi: 10.1172/JCI16198.
9
Assessing bone formation using mouse calvarial organ cultures.
Methods Mol Med. 2003;80:183-98. doi: 10.1385/1-59259-366-6:183.
10
Biochemical markers of bone formation in patients with plasma cell dyscrasias and benign osteoporosis.
Clin Chem. 2001 Apr;47(4):686-93.
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