INVESTIGATIONS ON THE REGULATION OF INTERVERTEBRAL DISC CELL MATRIX METALLOPROTEINASES

椎间盘退变是一种痛苦的致残状况，具有重大的社会经济后果。与椎间盘退变和背痛相关的医学问题，其严重程度足以让人去看医生，90%的人在一生中的某个时候都经历过。在男性中，背痛的发病率在生命的第三和第四个十年增加，在五十多岁时达到顶峰，此后下降。人口结构的变化表明，这一问题在今后几十年将更加严重。美国人口普查局的数据表明，在1990年至2010年间，45岁的人口数量将从8200万增加到1.24亿，在未来30年里，新兴国家的老年人数量也将增加200%至400%。在美国，背痛是人们看医生的第二大常见原因，与背痛相关的医疗条件比任何其他肌肉骨骼疾病都要多。尽管其发病率高，相关的丧失工作能力问题和经济影响，1992年澳大利亚每年耗资1亿美元，1999-2000年全球耗资1000亿美元（Dorland Data Networks， PA， USA），但腰痛的原因仍然知之甚少。在所有腰痛病例中，23-40%是由椎间盘疾病引起的。椎间盘源性腰痛的治疗目前是经验性的，要么通过改变生活方式来减少症状，要么通过手术切除或脊柱关节融合术来限制关节活动。基于我们最近的发现和过去16年同事们的发现，我们坚信，随着对疾病机制的更好理解和现代技术的使用，抑制、逆转或理想地预防椎间盘退变是可能的。没有这样的基础研究，就没有前瞻性治疗的科学基础。

Degeneration of the intervertebral disc is a painful disabling condition with major socioeconomic consequences. Medical problems associated with disc degeneration and back-pain, of sufficient severity to warrant consultation with a physician, are experienced by 90% of the population some time during their lives. In man, back pain increases in incidence in the third and fourth decades of life, peaks in the fifties and declines thereafter. Changes in population demographics indicate this problem will increase in severity over the next few decades. American Bureau of Census data indicate that between 1990 to 2010 the number of people >45 years will increase from 82 to 124 million, the number of elderly in emerging countries will also increase between 200 to 400% in the next 30 years. In the United States, back-pain is the second most common reason that people visit a physician and medical conditions related to back-pain account for more hospitalisations than any other musculoskeletal disorder. Despite its high incidence, associated problems of incapacity and economic implications, costed at $100 million per annum in Australia in 1992, and US$100 billion globally in 1999-2000 (Dorland Data Networks, PA, USA) the causes of low back-pain are still poorly understood. Disc disease is responsible for 23-40% of all cases of low back-pain. The management of discogenic low back-pain is currently empirical, directed either toward life-style changes to minimise symptomatology or to surgical resection or spinal arthrodesis to restrict articulation. Based on our recent findings and those of colleagues over the last 16 years, it is our strong conviction that it should be possible with a better understanding of disease mechanisms and with the use of modern technologies to inhibit, reverse or ideally prevent disc degeneration. Without such basic research there will be no scientific foundation upon which prospective therapies may be based.