Ciombor D McK, Aaron R K, Wang S, Simon B
Department of Orthopaedics, Brown Medical School, Providence, RI 02906, USA.
Osteoarthritis Cartilage. 2003 Jun;11(6):455-62. doi: 10.1016/s1063-4584(03)00083-9.
Hartley guinea pigs spontaneously develop arthritis that bears morphological, biochemical, and immunohistochemical similarities to human osteoarthritis. It is characterized by the appearance of superficial fibrillation by 12 months of age and severe cartilage lesions and eburnation by 18 months of age. This study examines the effect of treatment with a pulsed electromagnetic field (PEMF) upon the morphological progression of osteoarthritis in this animal model.
Hartley guinea pigs were exposed to a specific PEMF for 1h/day for 6 months, beginning at 12 months of age. Control animals were treated identically, but without PEMF exposure. Tibial articular cartilage was examined with histological/histochemical grading of the severity of arthritis, by immunohistochemistry for cartilage neoepitopes, 3B3(-) and BC-13, reflecting enzymatic cleavage of aggrecan, and by immunoreactivity to collagenase (MMP-13) and stromelysin (MMP-3). Immunoreactivity to TGFbeta, interleukin (IL)-1beta, and IL receptor antagonist protein (IRAP) antibodies was examined to suggest possible mechanisms of PEMF activity.
PEMF treatment preserves the morphology of articular cartilage and retards the development of osteoarthritic lesions. This observation is supported by a reduction in the cartilage neoepitopes, 3B3(-) and BC-13, and suppression of the matrix-degrading enzymes, collagenase and stromelysin. Cells immunopositive to IL-1 are decreased in number, while IRAP-positive cells are increased in response to treatment. PEMF treatment markedly increases the number of cells immunopositive to TGFbeta.
Treatment with PEMF appears to be disease-modifying in this model of osteoarthritis. Since TGFbeta is believed to upregulate gene expression for aggrecan, downregulate matrix metalloprotease and IL-1 activity, and upregulate inhibitors of matrix metalloprotease, the stimulation of TGFbeta may be a mechanism through which PEMF favorably affects cartilage homeostasis.
哈特利豚鼠会自发发展出关节炎，其在形态学、生物化学和免疫组织化学方面与人骨关节炎相似。其特征为在12月龄时出现表面纤维化，在18月龄时出现严重的软骨损伤和骨质象牙化。本研究考察了脉冲电磁场（PEMF）治疗对该动物模型中骨关节炎形态学进展的影响。
哈特利豚鼠从12月龄开始，每天接受特定的脉冲电磁场照射1小时，持续6个月。对照动物接受相同处理，但不进行脉冲电磁场照射。通过对关节炎严重程度进行组织学/组织化学分级、对反映聚集蛋白聚糖酶解的软骨新表位3B3(-)和BC-13进行免疫组织化学检测、以及对胶原酶（MMP-13）和基质溶解素（MMP-3）进行免疫反应性检测，来检查胫骨关节软骨。检测对转化生长因子β（TGFβ）、白细胞介素（IL）-1β和白细胞介素受体拮抗剂蛋白（IRAP）抗体的免疫反应性，以提示脉冲电磁场作用的可能机制。
脉冲电磁场治疗可保持关节软骨的形态，并延缓骨关节炎病变的发展。软骨新表位3B3(-)和BC-13减少，以及基质降解酶胶原酶和基质溶解素受到抑制，支持了这一观察结果。对IL-1呈免疫阳性的细胞数量减少，而对IRAP呈阳性的细胞数量因治疗而增加。脉冲电磁场治疗显著增加了对TGFβ呈免疫阳性的细胞数量。
在这个骨关节炎模型中，脉冲电磁场治疗似乎具有改善病情的作用。由于TGFβ被认为可上调聚集蛋白聚糖的基因表达、下调基质金属蛋白酶和IL-1的活性，并上调基质金属蛋白酶抑制剂，TGFβ的刺激可能是脉冲电磁场对软骨内环境稳定产生有利影响的一种机制。
