Associations of Serum Matrix Metalloproteinase-13 and Its Inhibitor Levels with Postmenopausal Osteoporosis_West China Medical Journal

Authors：

DAI Yi , YANG Huan , GAN Ning , WANG Zheng.

Department of Orthopedics, Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, P. R. China;

Corresponding author：

Keywords：

基质金属蛋白酶13; 组织金属蛋白酶抑制物1; 骨代谢; 骨质疏松; 绝经后

DOI：

10.7507/1002-0179.20130523

Video：

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目的　检测基质金属蛋白酶13（MMP-13）和组织金属蛋白酶抑制因子1（TIMP-1）的血清含量，分析其在妇女绝经后骨质疏松发病中的作用。方法　2009年3月－2012年9月选取武汉附近地区129例49～63岁绝经后妇女，根据双能X线吸收法检测的骨密度数值，分为正常组、低骨量组和骨质疏松组。采取酶联免疫吸附试验检测MMP-13、TIMP-1以及雌二醇（E2）、Ⅰ型原胶原N端前肽（PINP）和Ⅰ型胶原交联C末端肽（CTX）、骨保护蛋白（OPG）及其配体（OPGL）的含量，统计MMP-13/TIMP-1比值。结果　① 骨质疏松组中血清MMP-13水平[（44.25 ± 1.21） μg/L]高于正常组[（27.08 ± 1.41）μg/L]（P＜0.05）；② 骨质疏松组中血清MMP-13与骨密度、血清E2、OPGL水平存在明显负相关性（P＜0.05），和OPG、PINP和CTX存在明显正相关性（P＜0.05）；③ 低骨量组中MMP-13略高于骨质疏松组，且两者差异无统计学意义（P＞0.05），但是明显高于正常组（P＜0.05），同时与骨密度和血清E2、OPG、OPGL、PINP和CTX存在明显相关性（P＜0.05）。结论　血清MMP-13和MMP-13/TIMP-1比值与绝经后骨质疏松症妇女和绝经后低骨量组妇女骨代谢指标具有关联性。两者升高可能为绝经后妇女早期骨代谢尤其是胶原代谢过程增快的表现。

Citation： DAI Yi,YANG Huan,GAN Ning,WANG Zheng.. Associations of Serum Matrix Metalloproteinase-13 and Its Inhibitor Levels with Postmenopausal Osteoporosis. West China Medical Journal, 2013, 28(11): 1651-1654. doi: 10.7507/1002-0179.20130523 Copy

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13.	Yamagata K, Li X, Ikegaki S, et al. Dissection of Wnt5a-Ror2 signaling leading to matrix metalloproteinase (MMP-13) expression[J]. J Biol Chem, 2012, 287(2): 1588-1599.
14.	Patil A, Sable R, Kothari R. Genetic expression of MMP-Matrix-mettalo-proteinases (MMP-1 and MMP-13) as a function of anterior mandibular repositioning appliance on the growth of mandibular condylar cartilage with and without administration of insulin like growth factor (IGF-1) and transforming growth factor-B (TGF-β)[J]. Angle Orthod, 2012, 82(6): 1053-1059.
15.	Schmucker AC, Wright JB, Cole MD, et al. Distal interleukin-1β (IL-1β) response element of human matrix metalloproteinase-13 (MMP-13) binds activator protein 1 (AP-1) transcription factors and regulates gene expression[J]. J Biol Chem, 2012, 287(2): 1189-1197.
16.	Barthelemi S, Robinet J, Garnotel R, et al. Mechanical forces-induced human osteoblasts differentiation involves MMP-2/MMP-13/MT1-MMP proteolytic cascade[J]. J Cell Biochem, 2012, 113(3): 760-772.
17.	Lee YA, Choi HM, Lee SH, et al. Hypoxia differentially affects IL-1β-stimulated MMP-1 and MMP-13 expression of fibroblast-like synoviocytes in an HIF-1α-dependent manner[J]. Rheumatology, 2012, 51(3): 443-450.
18.	Schiltz C, Marty C, de Vernejoul MC, et al. Inhibition of osteoblastic metalloproteinases in mice prevents bone loss induced by oestrogen deficiency[J]. J Cell Biochem, 2008, 104(5): 1803-1817.
19.	Lewandowski KC, Komorowski J, O’Callaghan CJ, et al. Increased circulating levels of matrix metalloproteinase-2 and -9 in women with the polycystic ovary syndrome[J]. J Clin Endocrinol Metab, 2006, 91(3): 1173-1177.
20.	Yang H, Liu Q, Ahn JH, et al. Luteolin downregulates IL-1β-induced MMP-9 and -13 expressions in osteoblasts via inhibition of ERK signalling pathway[J]. J Enzyme Inhib Med Chem, 2012, 27(2): 261-266.

1. 　Manolagas SC. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis[J]. Endocr Rev, 2000, 21(2): 115-137.
2. 　Gali JC. Osteoporose[J]. Acta Ortop Bras, 2001, 9(6): 53-62.
3. 　Birkedal-Hansen EL. Role of matrix rnetalloproteinases in human periodontal diseases[J]. J Periodontol, 1993, 64(10): 474-484.
4. 　Altman RD. Criteria for classification of clinical osteoarthritis[J]. J Rheumatol, 1991, 18(9): 10-12.
5. 　徐苓. 骨质疏松症[M]. 上海: 上海科学技术出版社, 2011: 63.
6. 　Scotti C, Piccinini E, Takizawa H, et al. Engineering of a functional bone organ through endochondral ossification[J]. Proc Natl Acad Sci USA, 2013, 110(10): 3997-4002.
7. 　Sanchez C, Pesesse L, Gabay O, et al. Regulation of subchondral bone osteoblast metabolism by cyclic compression[J]. Arthritis Rheum, 2012, 64(4): 1193-1203.
8. 　Hirata M, Kugimiya F, Fukai A, et al. C/EBPβ and RUNX2 cooperate to degrade cartilage with MMP-13 as the target and HIF-2α as the inducer in chondrocytes[J]. Hum Mol Genet, 2012, 21(5): 1111-1123.
9. 　Wu MH, Lo JF, Kuo CH, et al. Endothelin-1 promotes MMP-13 production and migration in human chondrosarcoma cells through FAK/PI3K/Akt/mTOR pathways[J]. J Cell Physiol, 2012, 227(8): 3016-3026.
10. 　Pecchi E, Priam S, Mladenovic Z, et al. A potential role of chondroitin sulfate on bone in osteoarthritis:inhibition of prostaglandin E2 and matrix metalloproteinases synthesis in interleukin-1β-stimulated osteoblasts[J]. Osteoarthr Cartilage, 2012, 20(2): 127-135.
11. 　Kusano K, Miyaura C, Inada M, et al. Regulation of matrix metalloproteinases (MMP-2, -3, -9, and -13) by interleukin-1 and interleukin-6 in mouse calvaria: association of MMP induction with bone resorption[J]. Endocrinology, 1998, 139(3): 1338-1345.
12. 　DAI Y. Relationships between circulating matrix metallproteinase-3, tissue inhibitor of matrix metalloproteinase-1 levels and postmenopausal osteoporosis[J]. Bone, 2010, 47(S3): 389-390.
13. 　Yamagata K, Li X, Ikegaki S, et al. Dissection of Wnt5a-Ror2 signaling leading to matrix metalloproteinase (MMP-13) expression[J]. J Biol Chem, 2012, 287(2): 1588-1599.
14. 　Patil A, Sable R, Kothari R. Genetic expression of MMP-Matrix-mettalo-proteinases (MMP-1 and MMP-13) as a function of anterior mandibular repositioning appliance on the growth of mandibular condylar cartilage with and without administration of insulin like growth factor (IGF-1) and transforming growth factor-B (TGF-β)[J]. Angle Orthod, 2012, 82(6): 1053-1059.
15. 　Schmucker AC, Wright JB, Cole MD, et al. Distal interleukin-1β (IL-1β) response element of human matrix metalloproteinase-13 (MMP-13) binds activator protein 1 (AP-1) transcription factors and regulates gene expression[J]. J Biol Chem, 2012, 287(2): 1189-1197.
16. 　Barthelemi S, Robinet J, Garnotel R, et al. Mechanical forces-induced human osteoblasts differentiation involves MMP-2/MMP-13/MT1-MMP proteolytic cascade[J]. J Cell Biochem, 2012, 113(3): 760-772.
17. 　Lee YA, Choi HM, Lee SH, et al. Hypoxia differentially affects IL-1β-stimulated MMP-1 and MMP-13 expression of fibroblast-like synoviocytes in an HIF-1α-dependent manner[J]. Rheumatology, 2012, 51(3): 443-450.
18. 　Schiltz C, Marty C, de Vernejoul MC, et al. Inhibition of osteoblastic metalloproteinases in mice prevents bone loss induced by oestrogen deficiency[J]. J Cell Biochem, 2008, 104(5): 1803-1817.
19. 　Lewandowski KC, Komorowski J, O’Callaghan CJ, et al. Increased circulating levels of matrix metalloproteinase-2 and -9 in women with the polycystic ovary syndrome[J]. J Clin Endocrinol Metab, 2006, 91(3): 1173-1177.
20. 　Yang H, Liu Q, Ahn JH, et al. Luteolin downregulates IL-1β-induced MMP-9 and -13 expressions in osteoblasts via inhibition of ERK signalling pathway[J]. J Enzyme Inhib Med Chem, 2012, 27(2): 261-266.

West China Medical Journal

Associations of Serum Matrix Metalloproteinase-13 and Its Inhibitor Levels with Postmenopausal Osteoporosis

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