Attenuation of osteoarthritis via blockade of the SDF-1/CXCR4 signaling pathway.
Attenuation of osteoarthritis via blockade of the SDF-1/CXCR4 signaling pathway.
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通过阻断 SDF-1/CXCR4 信号通路减轻骨关节炎。
DOI：
10.1186/ar3930
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发表时间：
2012-07-31
影响因子：
4.9
通讯作者：
Chen Q
中科院分区：
文献类型：
--
作者：
Wei F;Moore DC;Wei L;Li Y;Zhang G;Wei X;Lee JK;Chen Q
本研究旨在评价在豚鼠骨关节炎（OA）模型中，通过AMD 3100破坏基质细胞衍生因子-1（SDF-1）/C-X-C趋化因子受体4型（CXCR 4）信号转导来减轻OA发病机制。在用SDF-1处理之前，将OA软骨细胞和软骨外植体与SDF-1、siRNA CXCR 4或抗CXCR 4抗体一起孵育。采用实时荧光定量聚合酶链反应（RT-PCR）和酶联免疫吸附试验（ELISA）分别检测基质金属蛋白酶（MMPs）mRNA和蛋白水平。将35只9月龄雄性Hartley豚鼠（0.88 kg ± 0.21 kg）分为3组：AMD治疗组（n = 13）、OA组（n = 11）和假手术组（n = 11）。治疗后3个月，收集膝关节、滑液和血清进行组织学和生化分析。采用改良的Mankin评分评估软骨损伤的严重程度。采用ELISA法测定SDF-1、糖胺聚糖（GAG）、MMP-1、MMP-13和白细胞介素-1（IL-1β）的水平。SDF-1浸润软骨并减少蛋白多糖染色。增加的糖胺聚糖和MMP-13活性被发现在培养基中响应SDF-1治疗。用siRNA CXCR 4或CXCR 4抗体破坏SDF-1和CXCR 4之间的相互作用减弱了SDF-1的作用。番红-O染色显示，与对照组动物相比，AMD 3100处理组动物的软骨损伤较少，Mankin评分最低。AMD 3100组关节液中SDF-1、GAG、MMP-1、MMP-13和IL-1β的水平明显低于对照组。SDF-1与CXCR 4的结合诱导OA软骨退变。分解代谢过程可以通过药物阻断SDF-1/CXCR 4信号传导来破坏。总之，这些发现提高了破坏SDF-1/CXCR 4信号传导可用作减轻软骨退变的治疗方法的可能性。
This study was performed to evaluate the attenuation of osteoarthritic (OA) pathogenesis via disruption of the stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4) signaling with AMD3100 in a guinea pig OA model. OA chondrocytes and cartilage explants were incubated with SDF-1, siRNA CXCR4, or anti-CXCR4 antibody before treatment with SDF-1. Matrix metalloproteases (MMPs) mRNA and protein levels were measured with real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The 35 9-month-old male Hartley guinea pigs (0.88 kg ± 0.21 kg) were divided into three groups: AMD-treated group (n = 13); OA group (n = 11); and sham group (n = 11). At 3 months after treatment, knee joints, synovial fluid, and serum were collected for histologic and biochemical analysis. The severity of cartilage damage was assessed by using the modified Mankin score. The levels of SDF-1, glycosaminoglycans (GAGs), MMP-1, MMP-13, and interleukin-1 (IL-1β) were quantified with ELISA. SDF-1 infiltrated cartilage and decreased proteoglycan staining. Increased glycosaminoglycans and MMP-13 activity were found in the culture media in response to SDF-1 treatment. Disrupting the interaction between SDF-1 and CXCR4 with siRNA CXCR4 or CXCR4 antibody attenuated the effect of SDF-1. Safranin-O staining revealed less cartilage damage in the AMD3100-treated animals with the lowest Mankin score compared with the control animals. The levels of SDF-1, GAG, MMP1, MMP-13, and IL-1β were much lower in the synovial fluid of the AMD3100 group than in that of control group. The binding of SDF-1 to CXCR4 induces OA cartilage degeneration. The catabolic processes can be disrupted by pharmacologic blockade of SDF-1/CXCR4 signaling. Together, these findings raise the possibility that disruption of the SDF-1/CXCR4 signaling can be used as a therapeutic approach to attenuate cartilage degeneration.
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影响因子：
8.8
作者：
通讯作者：
--
影响因子：
--
作者：
Lawrence, Reva C.;Felson, David T.;Wolfe, Frederick
通讯作者：
Wolfe, Frederick
影响因子：
4.9
作者：
Hendrix, CW;Flexner, C;Henson, GW
通讯作者：
Henson, GW
DOI：
10.1016/0304-4165(86)90306-5
发表时间：
1986-09-04
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FARNDALE, RW;BUTTLE, DJ;BARRETT, AJ
通讯作者：
BARRETT, AJ
影响因子：
7
作者：
Huebner, J. L.;Kraus, V. B.
通讯作者：
Kraus, V. B.