The role and mechanism of S100 calcium binding protein B in osteoarthritis cartilage damage repair_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

 ZHU Lifan , ZHOU Jianxin , ZENG Jincai , ZHANG Xiaojian , SHEN Pengcheng , WENG Fengbiao

Department of Orthopedics, First People’s Hospital of Wujiang District of Suzhou, Wujiang Hospital Affiliated to Nantong University, Wujiang Jiangsu, 215200, P.R.China;

Corresponding author：

ZHU Lifan, Email: zhulifan@live.cn

Keywords：

S100 calcium binding protein B; synovial fibroblasts; osteoarthritis; cartilage damage; fibroblast growth factor 2; fibroblast growth factor receptor 1

DOI：

10.7507/1002-1892.201804060

Video：

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Objective To investigate the role and mechanism of S100 calcium binding protein B (S100B) in osteoarthritis (OA) cartilage damage repair. Methods Twenty New Zealand rabbits were randomly divided into control group and model group, with 10 rabbits in each group. Rabbits in the model group were injured by the right knee joint immobilization method to make the artilage injury model, while the control group did not deal with any injury. After 4 weeks, the levels of interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) in synovial fluid were detected by ELISA method; the mRNA and protein expressions of S100B, fibroblast growth factor 2 (FGF-2), and FGF receptor 1 (FGFR1) in cartilage tissue were examined by real-time fluorescence quantitative PCR (qRT-PCR) and Western blot assay. Human synovial fibroblasts (SF) were isolated and cultured in vitro. The effects of S100B overexpression and knockdown on the levels of IL-1β and TNF-α (ELISA method) and the expressions of FGF-2 and FGFR1 gene (qRT-PCR) and protein (Western blot) were observed. Moreover, the effects of FGFR1 knockdown in above S100 overexpression system on the levels of IL-1β and TNF-α (ELISA method) and the expressions of FGF-2 and FGFR1 gene (qRT-PCR) and protein (Western blot) were observed. Results ELISA detection showed that the expressions of IL-1β and TNF-α in the synovial fluid of the model group were significantly higher than those of the control group (P<0.05); qRT-PCR and Western blot detection showed that the mRNA and protein expressions of S100B, FGF-2, and FGFR1 in cartilage tissue were significantly higher than those of the control group (P<0.05). Overexpression and knockdown S100 could respectively significantly increase and decrease lipopolysaccharides (LPS) induced IL-1β and TNF-α levels elevation and the mRNA and protein expressions of FGF-2 and FGFR1 (P<0.05); whereas FGFR1 knockdown could significantly decrease LPS induced IL-1β and TNF-α levels elevation and the mRNA and protein expressions of FGF-2 and FGFR1 (P<0.05). Conclusion S100B protein can regulate the inflammatory response of SF and may affect the repair of cartilage damage in OA, and the mechanism may be related to the activation of FGF-2/FGFR1 signaling pathway.

Citation： ZHU Lifan, ZHOU Jianxin, ZENG Jincai, ZHANG Xiaojian, SHEN Pengcheng, WENG Fengbiao. The role and mechanism of S100 calcium binding protein B in osteoarthritis cartilage damage repair. Chinese Journal of Reparative and Reconstructive Surgery, 2018, 32(11): 1429-1434. doi: 10.7507/1002-1892.201804060 Copy

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2.	Heijink A, Gomoll AH, Madry H, et al. Biomechanical considerations in the pathogenesis of osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc, 2012, 20(3): 423-435.
3.	Goldring MB, Otero M, Plumb DA, et al. Roles of inflammatory and anabolic cytokines in cartilage metabolism: signals and multiple effectors converge upon MMP-13 regulation in osteoarthritis. Eur Cell Mater, 2011, 21: 202-220.
4.	Montaseri A, Busch F, Mobasheri A, et al. IGF-1 and PDGF-bb Suppress IL-1β-Induced Cartilage Degradation through Down-Regulation of NF-κB Signaling: Involvement of Src/PI-3K/AKT Pathway. PLoS One, 2011, 6(12): e28663.
5.	Yan D, Chen D, Cool SM, et al. Fibroblast growth factor receptor 1 is principally responsible for fibroblast growth factor 2-induced catabolic activities in human articular chondrocytes. Arthritis Res Ther, 2011, 13(4): R130.
6.	Davidson D, Blanc A, Filion D, et al. Fibroblast growth factor (FGF) 18 signals through FGF receptor 3 to promote chondrogenesis. J Biol Chem, 2005, 280(21): 20509-20515.
7.	Zreiqat H, Belluoccio D, Smith MM, et al. S100A8 and S100A9 in experimental osteoarthritis. Arthritis Res Ther, 2010, 12(1): R16.
8.	Choi IY, Karpus ON, Turner JD, et al. Stromal cell markers are differentially expressed in the synovial tissue of patients with early arthritis. PLoS One, 2017, 12(8): e0182751.
9.	Abramson SB, Attur M. Developments in the scientific understanding of osteoarthritis. Arthritis Res Ther, 2009, 11(3): 227.
10.	Yammani RR. S100 proteins in cartilage: Role in arthritis. Biochim Biophys Acta, 2012, 1822(4): 600-606.
11.	Choi W, Kawanabe H, Sawa Y, et al. Effects of bFGF on suppression of collagen type I accumulation and scar tissue formation during wound healing after mucoperiosteal denudation of rat palate. Acta Odontol Scand, 2008, 66(1): 31-37.
12.	Deng T, Huang S, Zhou S, et al. Cartilage regeneration using a novel gelatin-chondroitin-hyaluronan hybrid scaffold containing bFGF-impregnated microspheres. J Microencapsul, 2007, 24(2): 163-174.
13.	Wang X, Manner PA, Horner A, et al. Regulation of MMP-13 expression by RUNX2 and FGF2 in osteoarthritic cartilage. Osteoarthritis Cartilage, 2004, 12(12): 963-973.
14.	Schmal H, Zwingmann J, Fehrenbach M, et al. bFGF influences human articular chondrocyte differentiation. Cytotherapy, 2007, 9(2): 184-193.
15.	Im HJ, Muddasani P, Natarajan V, et al. Basic fibroblast growth factor stimulates matrix metalloproteinase-13 via the molecular cross-talk between the mitogen-activated protein kinases and protein kinase Cdelta pathways in human adult articular chondrocytes. J Biol Chem, 2007, 282(15): 11110-11121.
16.	Muddasani P, Norman JC, Ellman M, et al. Basic fibroblast growth factor activates the MAPK and NFkappaB pathways that converge on Elk-1 to control production of matrix metalloproteinase-13 by human adult articular chondrocytes. J Biol Chem, 2007, 282(43): 31409-31421.
17.	Yan D, Chen D, Im HJ. Fibroblast growth factor-2 promotes catabolism via FGFR1-Ras-Raf-MEK1/2-ERK1/2 axis that coordinates with the PKCδ pathway in human articular chondrocytes. J Cell Biochem, 2012, 113(9): 2856-2865.

1. Allen KD, Golightly YM. State of the evidence. Curr Opin Rheumatol, 2015, 27(3): 276-283.
2. Heijink A, Gomoll AH, Madry H, et al. Biomechanical considerations in the pathogenesis of osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc, 2012, 20(3): 423-435.
3. Goldring MB, Otero M, Plumb DA, et al. Roles of inflammatory and anabolic cytokines in cartilage metabolism: signals and multiple effectors converge upon MMP-13 regulation in osteoarthritis. Eur Cell Mater, 2011, 21: 202-220.
4. Montaseri A, Busch F, Mobasheri A, et al. IGF-1 and PDGF-bb Suppress IL-1β-Induced Cartilage Degradation through Down-Regulation of NF-κB Signaling: Involvement of Src/PI-3K/AKT Pathway. PLoS One, 2011, 6(12): e28663.
5. Yan D, Chen D, Cool SM, et al. Fibroblast growth factor receptor 1 is principally responsible for fibroblast growth factor 2-induced catabolic activities in human articular chondrocytes. Arthritis Res Ther, 2011, 13(4): R130.
6. Davidson D, Blanc A, Filion D, et al. Fibroblast growth factor (FGF) 18 signals through FGF receptor 3 to promote chondrogenesis. J Biol Chem, 2005, 280(21): 20509-20515.
7. Zreiqat H, Belluoccio D, Smith MM, et al. S100A8 and S100A9 in experimental osteoarthritis. Arthritis Res Ther, 2010, 12(1): R16.
8. Choi IY, Karpus ON, Turner JD, et al. Stromal cell markers are differentially expressed in the synovial tissue of patients with early arthritis. PLoS One, 2017, 12(8): e0182751.
9. Abramson SB, Attur M. Developments in the scientific understanding of osteoarthritis. Arthritis Res Ther, 2009, 11(3): 227.
10. Yammani RR. S100 proteins in cartilage: Role in arthritis. Biochim Biophys Acta, 2012, 1822(4): 600-606.
11. Choi W, Kawanabe H, Sawa Y, et al. Effects of bFGF on suppression of collagen type I accumulation and scar tissue formation during wound healing after mucoperiosteal denudation of rat palate. Acta Odontol Scand, 2008, 66(1): 31-37.
12. Deng T, Huang S, Zhou S, et al. Cartilage regeneration using a novel gelatin-chondroitin-hyaluronan hybrid scaffold containing bFGF-impregnated microspheres. J Microencapsul, 2007, 24(2): 163-174.
13. Wang X, Manner PA, Horner A, et al. Regulation of MMP-13 expression by RUNX2 and FGF2 in osteoarthritic cartilage. Osteoarthritis Cartilage, 2004, 12(12): 963-973.
14. Schmal H, Zwingmann J, Fehrenbach M, et al. bFGF influences human articular chondrocyte differentiation. Cytotherapy, 2007, 9(2): 184-193.
15. Im HJ, Muddasani P, Natarajan V, et al. Basic fibroblast growth factor stimulates matrix metalloproteinase-13 via the molecular cross-talk between the mitogen-activated protein kinases and protein kinase Cdelta pathways in human adult articular chondrocytes. J Biol Chem, 2007, 282(15): 11110-11121.
16. Muddasani P, Norman JC, Ellman M, et al. Basic fibroblast growth factor activates the MAPK and NFkappaB pathways that converge on Elk-1 to control production of matrix metalloproteinase-13 by human adult articular chondrocytes. J Biol Chem, 2007, 282(43): 31409-31421.
17. Yan D, Chen D, Im HJ. Fibroblast growth factor-2 promotes catabolism via FGFR1-Ras-Raf-MEK1/2-ERK1/2 axis that coordinates with the PKCδ pathway in human articular chondrocytes. J Cell Biochem, 2012, 113(9): 2856-2865.

Chinese Journal of Reparative and Reconstructive Surgery

The role and mechanism of S100 calcium binding protein B in osteoarthritis cartilage damage repair

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