Pathobiology of the small leucine rich repeat proteoglycans in cartilage, intervertebral disc and tendon degeneration

软骨、椎间盘和肌腱变性中富含亮氨酸的小重复蛋白聚糖的病理学

• 批准号: nhmrc : 352562
• 负责人: Dr James Melrose
• 金额: $ 34.45万
• 依托单位: The University of Sydney
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2005
• 资助国家: 澳大利亚
• 起止时间: 2005-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/pathobiology-small-leucine-tendon-degeneration/81853
• 关键词: Pathobiology; small; leucine; rich; repeat

Back problems (M$700), OA (M$600), muscle and tendon disorders (M$500) accounted for 60% of musculoskeletal (MSK) health care expenditure in Australia in 1993-1994, were the second most common cause of presentations to a general practitioner, the third leading contributor to health system expenditure (>$3 billion) and accounted for ~300,000 hospital admissions, ~15 million medical services and over 13 million prescriptions. Significant disability due to MSK disease were noted in ~50% of people aged 65 years. Australian census data indicates that ageing trends will result in an increased incidence of MSK conditions as the longevity of the Australian population rises, exerting an ever increasing burden on the healthcare budget. Extreme levels of sporting or physical activity from traumatic loading of joints can lead to excessive loading of collagen fibres in MSK tissues leading to their failure and loss of tissue function. Common end stages of collagen fibre breakdown are preceded by matrix changes which may predispose MSK tissues to enzymatic and mechanical damage. One such change is an increased degradation of a family of small leucine-rich proteoglycans (SLRPs) which modulate the diameter, strength and assembly of collagen fibrils and bind and modify the effects of reparative growth factors and degradative cytokines within connective tissues. Altered synthesis of SLRPs and SLRP fragments have been identified in abnormal intervertebral disc, cartilage and tendon. Very little is known however about how these fragments are generated within these tissues and how they affect growth factor binding or collagen fibril formation. This deficiency will be addressed in our proposed study which will provide novel information on mechanisms of cartilage, intervertebral disc and tendon degeneration and potential therapeutic and diagnostic targets which may be exploited in future studies on the treatment of these musculoskeletal conditions.

1993-1994 年，背部问题（700 马币）、骨关节炎（600 马币）、肌肉和肌腱疾病（500 马币）占澳大利亚肌肉骨骼 (MSK) 医疗保健支出的 60%，是向全科医生就诊的第二大常见原因，是卫生系统支出的第三大原因（>30 亿美元），约 300,000 人住院，约 1500 万人次医疗服务和医疗费用。结束 1300 万张处方。大约 50% 的 65 岁人群因 MSK 疾病而出现严重残疾。澳大利亚人口普查数据表明，随着澳大利亚人口寿命的延长，老龄化趋势将导致 MSK 病症的发病率增加，从而给医疗预算带来越来越大的负担。关节创伤性负荷造成的极端运动或体力活动可能会导致 MSK 组织中胶原纤维负荷过度，从而导致组织功能衰竭和丧失。胶原纤维分解的常见终末阶段之前会发生基质变化，这可能会使 MSK 组织容易受到酶促和机械损伤。其中一个变化是富含亮氨酸的小蛋白多糖 (SLRP) 家族的降解增加，这些蛋白多糖调节胶原纤维的直径、强度和组装，并结合和改变结缔组织内修复性生长因子和降解细胞因子的作用。在异常椎间盘、软骨和肌腱中已发现 SLRP 和 SLRP 片段的合成发生改变。然而，人们对这些碎片如何在这些组织内产生以及它们如何影响生长因子结合或胶原纤维形成知之甚少。我们提出的研究将解决这一缺陷，该研究将提供有关软骨、椎间盘和肌腱退化机制的新信息，以及可能在未来治疗这些肌肉骨骼疾病的研究中利用的潜在治疗和诊断目标。