INVESTIGATIONS ON THE REGULATION OF INTERVERTEBRAL DISC CELL MATRIX METALLOPROTEINASES

椎间盘退变是一种痛苦的致残性疾病，具有重大的社会经济后果。与椎间盘退变和背痛相关的医疗问题，其严重程度足以保证向医生咨询，90%的人口在其一生中的某个时候经历过。在人类中，背痛的发病率在生命的第三和第四个十年中增加，在五十年代达到顶峰，此后下降。人口统计数据的变化表明，这个问题在未来几十年内将更加严重。美国人口普查局的数据表明，1990年至2010年间，45岁的人口数量将从82万增加到1.24亿，新兴国家的老年人数量也将在未来30年内增加200%至400%。在美国，背痛是人们去看医生的第二个最常见的原因，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，相关的丧失能力问题和经济影响，1992年在澳大利亚每年花费1亿美元，1999-2000年全球花费1000亿美元（Dorland Data Networks，PA，USA），但对腰痛的原因仍然知之甚少。椎间盘疾病占所有腰痛病例的23-40%。椎间盘源性下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疼痛，要么通过手术切除或脊柱关节融合来限制关节活动。基于我们最近的研究结果和过去16年来的同事们的研究结果，我们坚信，通过更好地了解疾病机制，并利用现代技术来抑制，逆转或理想地预防椎间盘退变应该是可能的。没有这样的基础研究，就没有可能作为前瞻性治疗基础的科学基础。

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.