Expanding the adipokine network in cartilage: identification and regulation of novel factors in human and murine chondrocytes
Expanding the adipokine network in cartilage: identification and regulation of novel factors in human and murine chondrocytes
复制标题
DOI：
10.1136/ard.2010.132399
复制
发表时间：
2011-03-01
影响因子：
27.4
通讯作者：
Gualillo, Oreste
中科院分区：
文献类型：
--
作者：
Conde, Javier;Gomez, Rodolfo;Gualillo, Oreste
背景肥胖是许多疾病的主要危险因素，包括与软骨破坏相关的关节紊乱。目的研究新的脂肪因子趋化蛋白Lcn2和血清淀粉样蛋白A3(SAA3)在小鼠和人软骨细胞中的表达，以及在基础条件下、多种生物和药物治疗以及软骨细胞分化过程中的表达。方法采用实时定量逆转录聚合酶链式反应(RT-PCR)和免疫印迹分析(Western印迹)检测新的脂肪因子趋化蛋白Lcn2和SAA3在ATDC-5小鼠软骨细胞系中的表达。人永生化软骨细胞系(T/C-28a2)和原代培养的人软骨细胞。白介素1β是这些新型脂肪因子的有效诱导剂。此外，地塞米松、脂多糖和其他相关脂肪因子如瘦素和脂联素单独和联合应用均能调节趋化蛋白、Lcn2和SAA3mRNA的表达。参与IL-1β介导的Lcn2和SAA3上调的细胞内信号转导通路包括Janus激酶(JAK)2、磷脂酰肌醇3-激酶(PI3K)和丝裂原活化蛋白(MAP)激酶。结论趋化蛋白、Lcn2和SAA3参与了软骨细胞的病理生理过程，并受IL-1β、脂联素和瘦素等脂肪因子的调节。JAK2、PI3K和MAP激酶可能参与了这些反应的调节。
Background Obesity is a major risk factor for a plethora of diseases including joint disorders associated with cartilage destruction. Recently, it has been demonstrated that adipose tissue might contribute to degenerative joint diseases via the secretion of potent bioactive molecules termed adipokines.Objective To study expression of the novel adipokines chemerin, lipocalin 2 (LCN2) and serum amyloid A3 (SAA3) in murine and human chondrocytes, under basal conditions, in response to a range of biological and pharmacological treatments, and during chondrocyte differentiation.Methods Chemerin, LCN2 and SAA3 mRNA and protein expression were evaluated by quantitative real-time reverse transcription PCR and western blot analysis, respectively, in the ATDC-5 murine chondrocyte cell line, a human immortalised chondrocyte cell line (T/C-28a2) and primary cultured human chondrocytes.Results Human and murine chondrocytes expressed chemerin, LCN2 and SAA3 mRNA; interleukin (IL)-1 beta was a potent inducer of these novel adipokines. Moreover, dexamethasone, lipopolysaccharides (LPS) and other relevant adipokines such as leptin and adiponectin were able to modulate chemerin, LCN2 and SAA3 mRNA expression alone and when coadministered. Intracellular signal transducers involved in the IL-1 beta-mediated upregulation of LCN2 and SAA3 included Janus kinase (JAK) 2, phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein (MAP) kinases. Finally, expression of chemerin, LCN2 and SAA3 mRNA expression were modulated throughout chondrocyte differentiation.Conclusion Chemerin, LCN2 and SAA3 are implicated in chondrocyte pathophysiology, and regulated by other relevant factors that drive inflammatory process such as IL-1 beta, LPS and adipokines including leptin and adiponectin. It seems likely that JAK2, PI3K and MAP kinases are involved in mediating these responses.