Role of vascular cell adhesion molecule-1 in abnormal differentiation of chondrocytes in Kaschin-Beck disease / 中华地方病学杂志

ABSTRACT

Objective To investigate the expression of vascular cell adhesion molecule-1 (VC.AM-1) in oxidative stress induced hypertrophic chondrocytes,in Kaschin-Beck disease (KBD) patients and in rat fed with T-2 toxin under selenium deficient conditions in order to analyze the relationship between VCAM-1 biological function and the dysregulation of chondrocyte differentiation in KBD.Methods The ATDC5 was cultured in 1％ ITS solution (10 mg/L insulin,5.5 mg/L transferrin,and 6.7 μg/L sodium selenite) for 21 days,and stimulated with 3-morpholino-sydnonimine (SIN-1,a nitric oxide [NO] donor) to obtain the oxidative stress induced hypertrophic chondrocytes.Real-time PCR was used to detect VCAM-1 mRNA in hypertrophic chondrocytes induced by different concentrations of SIN-1.The expressions of VCAM-I in articular cartilage of child and adult KBD patients and KBD animal model were determined via the immunohistochemical method,and KBD cartilage samples were obtained in KBD areas from KBD child who had died or from adults who had had surgery.Results After treatment of hypertrophic chondrocytes (ATCD5 cells) with SIN-1 (0,1,3,5 mmol/L),VCAM-1 mRNA levels (1.00 + 0.00,1.22 ± 0.20,0.71 ± 0.22,0.37 ± 0.16) were decreased in a dose-dependent manner when compared with the control group (F =27.788,P ＜ 0.05).The densities of VCAM-1 positive cells in superficial and middle zones of the articular cartilage of children KBD patients [(16.08 ± 5.20)％,(19.20 ± 9.71)％] were higher than those of control group [(0.00 ± 0.00)％,(0.00 ± 0.00)％],while that in the deep zone [(7.00 ± 4.40)％] in children KBD patients was significantly lower than that of control [(51.60 ± 20.58)％,tS/M/D=-10.972,-6.249,6.564,P ＜ 0.05].The positive cell density of VCAM-1 in the adult patients was significantly increased in the superficial zone [(7.92 ± 4.29)％ vs (3.12 ± 1.12)％] but significantly decreased in the middle zone [(17.54 ± 8.27)％ vs (31.75 ± 13.30)％] of articular cartilage when compared with that of control group (tS/D =-3.824,3.037,P ＜ 0.05).In articular cartilage of the four groups of KBD rats,the density of VCAM-1 positive cells in the superficial zone was significantly higher in low selenium diet group,T-2 toxin diet group and selenium deficient plus T-2 toxin diet group [(4.11 ± 1.90)％,(5.00 ±2.02)％,(2.78 ± 1.48)％ vs (1.89 ± 1.76)％,P ＜ 0.05].But the density of VCAM-1 positive cells in the deep zone was significantly lower in rat feed with selenium diet and selenium deficient plus T-2 toxin diet [(13.67 ± 2.45)％,(20.56 ± 7.42)％] than that of control group [(33.00 ± 12.57)％,P ＜ 0.05] in the epiphyseal cartilage of KBD rats.Conclusions The level of VCAM-1 is decreased both in the SIN-1 induced hypertrophic chondrocytes and in the deep zone of articular cartilage in KBD patients and in rat fed with T-2 toxin and selenium-deficient diets.VCAM-1 may be associated with the death of deep zone chondrocytes and differentiation disorder in cartilage.