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：

基質金屬蛋白酶13; 組織金屬蛋白酶抑制物1; 骨代謝; 骨質疏松; 絕經后

DOI：

10.7507/1002-0179.20130523

Video：

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目的　檢測基質金屬蛋白酶13（MMP-13）和組織金屬蛋白酶抑制因子1（TIMP-1）的血清含量，分析其在婦女絕經后骨質疏松發病中的作用。方法　2009年3月－2012年9月選取武漢附近地區129例49～63歲絕經后婦女，根據雙能X線吸收法檢測的骨密度數值，分為正常組、低骨量組和骨質疏松組。采取酶聯免疫吸附試驗檢測MMP-13、TIMP-1以及雌二醇（E2）、Ⅰ型原膠原N端前肽（PINP）和Ⅰ型膠原交聯C末端肽（CTX）、骨保護蛋白（OPG）及其配體（OPGL）的含量，統計MMP-13/TIMP-1比值。結果　① 骨質疏松組中血清MMP-13水平[（44.25 ± 1.21） μg/L]高于正常組[（27.08 ± 1.41）μg/L]（P＜0.05）；② 骨質疏松組中血清MMP-13與骨密度、血清E2、OPGL水平存在明顯負相關性（P＜0.05），和OPG、PINP和CTX存在明顯正相關性（P＜0.05）；③ 低骨量組中MMP-13略高于骨質疏松組，且兩者差異無統計學意義（P＞0.05），但是明顯高于正常組（P＜0.05），同時與骨密度和血清E2、OPG、OPGL、PINP和CTX存在明顯相關性（P＜0.05）。結論　血清MMP-13和MMP-13/TIMP-1比值與絕經后骨質疏松癥婦女和絕經后低骨量組婦女骨代謝指標具有關聯性。兩者升高可能為絕經后婦女早期骨代謝尤其是膠原代謝過程增快的表現。

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. 骨質疏松癥[M]. 上海: 上海科學技術出版社, 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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