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Chondrocyte Apoptosis and Expression of Bcl-2, Bax, Fas, and iNOS in Articular Cartilage in Patients with Kashin-Beck Disease

SHI JIE WANG, XIONG GUO, HONG ZUO, YIN GANG ZHANG, PENG XU, ZHI GUANG PING, ZENTIE ZHANG, and DONG GENG

ABSTRACT.

Objective.
Kashin-Beck disease (KBD) is a chronic, endemic osteochondropathy principally occurring in children. We investigated apoptotic chondrocyte death and the expression of Bcl-2, Bax, Fas, and inducible nitric oxide synthase (iNOS) in articular cartilage from patients with KBD in order to determine the pathogenesis of chondronecrosis in KBD.

Methods. Samples of articular cartilage were divided into 2 groups: control children (15 samples from 15 cases), and children with KBD (15 samples from 15 cases). KBD patients were diagnosed according to "Pathological Criteria to Diagnose KBD in China." Chondrocyte apoptosis was detected by TUNEL staining, and Bcl-2, Bax, Fas, and iNOS-positive articular chondrocytes were stained by immunohistochemistry. Articular cartilage was classified in 3 zones, and positive findings were counted by light microscopy for cytoplasmic staining by polyclonal antibodies of Bcl-2, Bax, Fas, and iNOS and apoptotic chondrocytes by TUNEL.

Results. The percentage of positive apoptotic chondrocytes stained by TUNEL in the middle zone of articular cartilage from the KBD patient group (33.60% ± 2.71%) was higher than that of controls (1.33% ± 0.41%; p < 0.01). The percentages of chondrocytes staining for Bcl-2, Bax, Fas, and iNOS in KBD patients were significantly higher than in controls (p < 0.01); the remarkable difference in Bcl-2, Bax, Fas, and iNOS expression among the upper, middle, and deep cartilage zones was also seen in KBD articular cartilage (p < 0.01); and staining for Bcl-2, Bax, Fas, and iNOS in KBD patients was prominent in the upper zone (41.93% ± 12.26%, 45.60% ± 15.78%, 53.60% ± 16.49%, 45.47% ± 14.02%, respectively) and the middle zone (14.93% ± 3.50%, 13.87% ± 4.32%, 23.27% ± 4.83%, 21.67% ± 6.82%) of articular cartilage.

Conclusion. The apoptotic chondrocytes and Bcl-2, Bax, Fas, and iNOS-positive chondrocytes were significantly more numerous in patients with KBD than in controls. (J Rheumatol 2006;33:615–9)

Key Indexing Terms:

KASHIN-BECK DISEASE
CHONDROCYTE
APOPTOSIS
Bcl-2
FAS
BAX
INDUCIBLE NITRIC OXIDE SYNTHASE


From the Key Laboratory of Environment and Gene Related Diseases, Xi'an Jiaotong University, Ministry of Education; and the Department of Imaging, Second Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.

Supported by the National Natural Science Foundation of China (No. 30371252, 30571616, 2002BA711A08) and the Natural Science Foundation of Xi'an Jiaotong University (No. XJJ-2004133).

S.J. Wang, MD, PhD, Department of Imaging, Second Hospital of Xi'an Jiaotong University; X. Guo, MD, Professor; H. Zuo, MD, PhD; Y.G. Zhang, MD, PhD; P. Xu, MD, PhD; Z.G. Ping, MD, PhD; Z. Zhang, Technician; D. Geng, Technician, Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University.

Address reprint requests to Dr. X. Guo, Medical School of Xi'an Jiaotong University, No. 76 West Road of Yanta, Xi'an 710061, China. E-mail: guoxiong_xjtu@163.net

Accepted for publication October 19, 2005.


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