INFLUENCE ON MATRIX METALLOPROTEINASES 3, 9, AND 13 LEVELS AFTER BLOCKING STROMAL CELL DERIVED FACTOR 1/CHEMOKINE RECEPTOR 4 SIGNALING PATHWAY WITH AMD3100_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

LI Yanlin ¹ , WANG Guoliang ¹ , CAO Bin ² , GAO Gang ¹ , MA Ke ¹ , CHEN Wendong ¹ , XU Peng ¹ , YANG Guang ¹

1Department of Sports Medicine, the First Hospital Affiliated to Kunming Medical University, Kunming Yunnan, 650000, P.R.China;;
2Department of Orthopedics, Second People’s Hospital of Hunan Province.;

Corresponding author：

Keywords：

Stromal cell derived factor 1; Chemokine receptor 4; Matrix metalloproteinase; Osteoarthritis

Video：

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Objective To investigate the influence on matrix metalloproteinases (MMP) 3, 9, and 13 levels of human articular cartilage cells after blocking stromal cell derived factor 1 (SDF-1)/ chemokine receptor 4 (CXCR4) signaling pathway with
AMD3100 and to define the function mechanism of AMD3100. Methods A total of 144 cartilage blocks from 12 osteoarthritis (OA) patients undergoing total knee arthroplasty (OA cartilage group) and 144 normal cartilage blocks (Mankin score of 0 or 1) from 12 patients undergoing traumatic amputation (normal cartilage group). OA cartilage group was further divided into subgroups A1, B1, and C1, and normal cartilage group into subgroups A2, B2, and C2. The cartilage tissues were cultured in DMEM solution containing 100 ng/mL SDF-1 and 1 000 nmol/L AMD3100 in subgroup A, 100 ng/mL SDF-1 and 1 000 nmol/L MAB310 in subgroup B, and 100 ng/mL SDF-1 in subgroup C, respectively. The levels of MMP-3, 9, and 13 were measured by ELISA; the expressions of MMP-3, 9, and 13mRNA were tested by RT-PCR. Results ELISA and RT-PCR results showed that the levels of MMP-3, 9, and 13 and the expressions of MMP-3, 9, and 13 mRNA were significantly lower in subgroup A than in subgroups B and C at the same time points (P lt; 0.05); the levels of MMP-3, 9, and 13 and the expressions of MMP-3, 9, and 13 mRNA were significantly higher in OA cartilage group than in normal cartilage group at the same time points (P lt; 0.05). Conclusion SDF-1 could induce overexpression and release of MMP-3, 9, and 13 in the articular cartilage through the SDF-1/CXCR4 signaling pathway; AMD3100 could reduce the mRNA expressions and secretion of MMP-3, 9, and 13 in OA cartilage by blocking the SDF-1/CXCR4 signaling pathway; but AMD3100 could not make the secretion of MMP-3, 9, and 13 return to normal levels in OA cartilage.

Citation： LI Yanlin,WANG Guoliang,CAO Bin,GAO Gang,MA Ke,CHEN Wendong,XU Peng,YANG Guang. INFLUENCE ON MATRIX METALLOPROTEINASES 3, 9, AND 13 LEVELS AFTER BLOCKING STROMAL CELL DERIVED FACTOR 1/CHEMOKINE RECEPTOR 4 SIGNALING PATHWAY WITH AMD3100. Chinese Journal of Reparative and Reconstructive Surgery, 2012, 26(6): 652-656. doi: Copy

1.	Elsaid KA, Machan JT, Waller K, et al. The impact of anterior cruciate ligament injury on lubricin metabolism and the effect of inhibiting tumor necrosis factor alpha on chondroprotection in an animal model. Arthritis Rheum, 2009, 60(10): 2997-3006.
2.	Hendren L, Beeson P. A review of the differences between normal and osteoarthritis articular cartilage in human knee and ankle joints. The Foot, 2009, 19(3): 171-176.
3.	Wei L, Sun X, Kanbe K, et al. Chondrocyte death induced by pathological concentration of chemokine Stromal cell-derived factor-1. J Rheumatol, 2006, 33(9): 1818-1826.
4.	Lisgnoli G, Toneguzzi S, Piacentini A, et al. CXCL12 (SDF-1) and CXCL13 (BCA-1) chemokines significantly induce proliferation and collagen type I expression in osteoblasts from osteoarthritis patients. J Cell Physiol, 2006, 206(1): 78-85.
5.	Ross JM, Sherwin AF, Poole CA. In vitro culture of enzymatieally isolated ehondron: a possible model for the initiation of osteoarthritis. J Anat, 2006, 209(6): 793-806.
6.	Altman RD. The classification of osteoarthritis. J Rheumatol Suppl, 1995, 43: 42-43.
7.	Flannery CR, Little CB, Caterson B, et al. Effects of culture conditions and exposure to catabolic stimulators (IL-1 and retinoic acid) on the expression of matrix metalloproteinases (MMPs) and disintegrin metalloproteinases (ADAMs) by articular cartilage chondrocytes. Matrix Biol, 1999, 18(3): 225-237.
8.	Mitchell PG, Mogna HA, Reeves LM, et al. Cloning, expression and type Ⅱ collagenolytic activity of matrix metalloprpteinase-13 from human osteoarthritis cartilage. J Clin Invest, 1996, 97(3): 761-768.
9.	班吉鹤, 周利武, 毛广平, 等. 应用蛋白质芯片检测骨性关节炎患者基质金属蛋白酶-13的初步研究. 医学研究生学报, 2008, 21(8): 836-838, 844.
10.	Kanbe K, Takagishi K, Chen Q. Stimulation of matrix metalloprotease 3 release from human chondrocytes by the interaction of stromal cell-derived factor 1 and CXC chemokine receptor 4. Arthritis Rheum, 2002, 46(1): 130-137.
11.	D’APuzzo M, Rolink A, Loetscher M, et al. The chemokine SDF-l, stromal cell-derivcd factor 1, attracts early stage B cell precursors via the chemokine receptor CXCR4. Eur J Immunol, 1997, 27(7): 1788-1793.
12.	Santiago B, Baleux F, Palao G, et al. CXCL12 is displayed by rheumatoid endothelial cells through its basic amino-terminal motif on heparan sulfate proteoglycans. Arthritis Res Ther, 2006, 8(2): R43.
13.	Chiu YC, Yang RS, Hsieh KH, et al. Stromal cell-derived factor-1 induces matrix metalloprotease-13 expression in human chondrocytes. Mol Pharmacol, 2007, 72(3): 695-703.
14.	Matthys P, Hatse S, Vermeire, et al. AMD3100, a potent and specific antagonist of the stromal cell-derived factor-1 chemokine receptor CXCR4, inhibits autoimmune joint inflammation in IFN-gamma receptor deficient mice. J Immunology, 2001, 167(8): 4686-4692.
15.	Blanco J, Barretina J, Henson G, et al. The CXCR4 antagonist AMD3100 efficiently inhibits cell-surface-expressed human immunodeficiency virus type 1 envelope-induced apoptosis. Antimicrob Agents Chemother, 2000, 44(1): 51-56.
16.	Hatse S, Princen K, Bridger G, et al. Chemokine receptor inhibition by AMD3100 is strictly confined to CXCR4. FEBS Lett, 2002, 527(1-3): 255-262.
17.	De Clercq E. The bicyclam AMD3100 story. Nat Rev Drug Discov, 2003, 2(7): 581-587.
18.	李晓林, 李彦林, 马珂, 等. SDF-1/CXCR4信号通路在骨性关节炎病理进程中的作用. 中国组织工程研究与临床康复, 2011, 15(15): 2805-2808.
19.	Tamamura H, Tsutsumi H, Masuno H, et al. Development of low molecular weight CXCR4 antagonists by exploratory structural tuning of cyclic tetra and pentapeptide-scaffolds towards the treatment of HIV infection, cancer metastasis and rheumatoid arthritis. Curr Med Chem, 2007, 14(1): 93-102.
20.	De Klerck B, Geboes L, Hatse S, et al. Pro-inflammatory properties of stromal cell-derived factor-1 (CXCL12) in collagen-induced arthritis. Arthritis Res Ther, 2005, 7(6): R1208-1220.

1. Elsaid KA, Machan JT, Waller K, et al. The impact of anterior cruciate ligament injury on lubricin metabolism and the effect of inhibiting tumor necrosis factor alpha on chondroprotection in an animal model. Arthritis Rheum, 2009, 60(10): 2997-3006.
2. Hendren L, Beeson P. A review of the differences between normal and osteoarthritis articular cartilage in human knee and ankle joints. The Foot, 2009, 19(3): 171-176.
3. Wei L, Sun X, Kanbe K, et al. Chondrocyte death induced by pathological concentration of chemokine Stromal cell-derived factor-1. J Rheumatol, 2006, 33(9): 1818-1826.
4. Lisgnoli G, Toneguzzi S, Piacentini A, et al. CXCL12 (SDF-1) and CXCL13 (BCA-1) chemokines significantly induce proliferation and collagen type I expression in osteoblasts from osteoarthritis patients. J Cell Physiol, 2006, 206(1): 78-85.
5. Ross JM, Sherwin AF, Poole CA. In vitro culture of enzymatieally isolated ehondron: a possible model for the initiation of osteoarthritis. J Anat, 2006, 209(6): 793-806.
6. Altman RD. The classification of osteoarthritis. J Rheumatol Suppl, 1995, 43: 42-43.
7. Flannery CR, Little CB, Caterson B, et al. Effects of culture conditions and exposure to catabolic stimulators (IL-1 and retinoic acid) on the expression of matrix metalloproteinases (MMPs) and disintegrin metalloproteinases (ADAMs) by articular cartilage chondrocytes. Matrix Biol, 1999, 18(3): 225-237.
8. Mitchell PG, Mogna HA, Reeves LM, et al. Cloning, expression and type Ⅱ collagenolytic activity of matrix metalloprpteinase-13 from human osteoarthritis cartilage. J Clin Invest, 1996, 97(3): 761-768.
9. 班吉鹤, 周利武, 毛广平, 等. 应用蛋白质芯片检测骨性关节炎患者基质金属蛋白酶-13的初步研究. 医学研究生学报, 2008, 21(8): 836-838, 844.
10. Kanbe K, Takagishi K, Chen Q. Stimulation of matrix metalloprotease 3 release from human chondrocytes by the interaction of stromal cell-derived factor 1 and CXC chemokine receptor 4. Arthritis Rheum, 2002, 46(1): 130-137.
11. D’APuzzo M, Rolink A, Loetscher M, et al. The chemokine SDF-l, stromal cell-derivcd factor 1, attracts early stage B cell precursors via the chemokine receptor CXCR4. Eur J Immunol, 1997, 27(7): 1788-1793.
12. Santiago B, Baleux F, Palao G, et al. CXCL12 is displayed by rheumatoid endothelial cells through its basic amino-terminal motif on heparan sulfate proteoglycans. Arthritis Res Ther, 2006, 8(2): R43.
13. Chiu YC, Yang RS, Hsieh KH, et al. Stromal cell-derived factor-1 induces matrix metalloprotease-13 expression in human chondrocytes. Mol Pharmacol, 2007, 72(3): 695-703.
14. Matthys P, Hatse S, Vermeire, et al. AMD3100, a potent and specific antagonist of the stromal cell-derived factor-1 chemokine receptor CXCR4, inhibits autoimmune joint inflammation in IFN-gamma receptor deficient mice. J Immunology, 2001, 167(8): 4686-4692.
15. Blanco J, Barretina J, Henson G, et al. The CXCR4 antagonist AMD3100 efficiently inhibits cell-surface-expressed human immunodeficiency virus type 1 envelope-induced apoptosis. Antimicrob Agents Chemother, 2000, 44(1): 51-56.
16. Hatse S, Princen K, Bridger G, et al. Chemokine receptor inhibition by AMD3100 is strictly confined to CXCR4. FEBS Lett, 2002, 527(1-3): 255-262.
17. De Clercq E. The bicyclam AMD3100 story. Nat Rev Drug Discov, 2003, 2(7): 581-587.
18. 李晓林, 李彦林, 马珂, 等. SDF-1/CXCR4信号通路在骨性关节炎病理进程中的作用. 中国组织工程研究与临床康复, 2011, 15(15): 2805-2808.
19. Tamamura H, Tsutsumi H, Masuno H, et al. Development of low molecular weight CXCR4 antagonists by exploratory structural tuning of cyclic tetra and pentapeptide-scaffolds towards the treatment of HIV infection, cancer metastasis and rheumatoid arthritis. Curr Med Chem, 2007, 14(1): 93-102.
20. De Klerck B, Geboes L, Hatse S, et al. Pro-inflammatory properties of stromal cell-derived factor-1 (CXCL12) in collagen-induced arthritis. Arthritis Res Ther, 2005, 7(6): R1208-1220.

Chinese Journal of Reparative and Reconstructive Surgery

INFLUENCE ON MATRIX METALLOPROTEINASES 3, 9, AND 13 LEVELS AFTER BLOCKING STROMAL CELL DERIVED FACTOR 1/CHEMOKINE RECEPTOR 4 SIGNALING PATHWAY WITH AMD3100

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