Lisignoli G, Grassi F, Piacentini A, Cocchini B, Remiddi G, Bevilacqua C, Facchini A
Laboratorio di Immunologia e Genetica, Istituti Ortopedici Rizzoli, Bologna, Italy.
Osteoarthritis Cartilage. 2001 Feb;9(2):161-8. doi: 10.1053/joca.2000.0372.
Many studies have evidenced the clinical efficacy of hyaluronan (HA) in the treatment of osteoarthritis (OA). However, human and animal studies have described proinflammatory effects of HA on cells not involved in OA. We therefore investigated whether different molecular weight HA preparations can affect proinflammatory cytokine (IL1beta and TNFalpha) or chemokine (IL8, MCP-1 and RANTES) expression in human chondrocytes and synoviocytes isolated from OA patients.
Human chondrocytes and synoviocytes were cultured in vitro in the presence or absence of three different purified HA pharmaceutical preparations (1x10(6) Kd, 5x10(5) Kd and 6.5x10(4) Kd) and assessed for the production of proinflammatory cytokines and chemokines and their mRNA expression.
basal conditions, both chondrocytes and synoviocytes produce only MCP-1 and IL8, along with low quantities of IL1beta and TNFalpha, but not RANTES. IL8 production was generally about 100 times higher in chondrocytes than in synoviocytes, while MCP-1 was roughly twice as high in synoviocytes than in chondrocytes. At the mRNA level, expression of IL1beta, TNFalpha, IL8, MCP-1 and RANTES did not change in the presence of the three HA preparations either in synoviocytes or in chondrocytes with respect to basal condition. None of the three different HA preparations significantly affected production of IL8 or MCP-1.
These data demonstrate that preparations of HA of the same origin but with different MWs do not induce proinflammatory cytokines and chemokines expressed by chondrocytes and synoviocytes that are either directly or indirectly involved in OA progression.
许多研究已证实透明质酸(HA)治疗骨关节炎(OA)的临床疗效。然而,人体和动物研究描述了HA对未参与OA的细胞的促炎作用。因此,我们研究了不同分子量的HA制剂是否会影响从OA患者分离的人软骨细胞和滑膜细胞中促炎细胞因子(IL-1β和TNF-α)或趋化因子(IL-8、MCP-1和RANTES)的表达。
将人软骨细胞和滑膜细胞在有或无三种不同纯化的HA药物制剂(1×10⁶ Kd、5×10⁵ Kd和6.5×10⁴ Kd)存在的情况下进行体外培养,并评估促炎细胞因子和趋化因子的产生及其mRNA表达。
在基础条件下,软骨细胞和滑膜细胞均仅产生MCP-1和IL-8,以及少量的IL-1β和TNF-α,但不产生RANTES。软骨细胞中IL-8的产生通常比滑膜细胞高约100倍,而滑膜细胞中MCP-1的产生约为软骨细胞中的两倍。在mRNA水平上,相对于基础条件,三种HA制剂存在时,滑膜细胞或软骨细胞中IL-1β、TNF-α、IL-8、MCP-1和RANTES的表达均未改变。三种不同的HA制剂均未显著影响IL-8或MCP-1的产生。
这些数据表明,相同来源但不同分子量的HA制剂不会诱导直接或间接参与OA进展的软骨细胞和滑膜细胞表达促炎细胞因子和趋化因子。