Rani Shobha, Barbe Mary F, Barr Ann E, Litvin Judith
Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Bone. 2009 Mar;44(3):502-12. doi: 10.1016/j.bone.2008.11.012. Epub 2008 Nov 27.
Work-related musculoskeletal disorders (WMSDs), also known as overuse injuries, account for a substantial proportion of work injuries and workers' compensation claims in the United States. However, the pathophysiological mechanisms underlying WMSDs are not well understood, especially the early events in their development. In this study we used an animal model of upper extremity WMSD, in which rats perform a voluntary repetitive reaching and pulling task for a food reward. This innovative model provides us an opportunity to investigate the role of molecules which may be used either as markers of early diagnosis of these disorders, and/or could be targeted for therapeutic purposes in the future. Periostin-like-factor (PLF), and Periostin were examined in this study. Both belong to a family of vitamin K-dependent gamma carboxylated proteins characterized by the presence of conserved Fasciclin domains and not detected in adult tissues except under conditions of chronic overload, injury, stress or pathology. The spatial and temporal pattern of PLF and Periostin localization was examined by immunohistochemistry and western blot analysis in the radius and ulna of animals performing a high repetition, high force task for up to 12 weeks and in controls. We found that PLF was present primarily in the cellular periosteum, articular cartilage, osteoblasts, osteocytes and osteoclasts at weeks 3 and 6 in all distal bone sites examined. This increase coincided with a transient increase in serum osteocalcin in week 6, indicative of adaptive bone formation at this time point. PLF immunoexpression decreased in the distal periosteum and metaphysis by week 12, coincided temporally with an increase in serum Trap5b, thinning of the growth plate and reduced cortical thickness. In contrast to PLF, once Periostin was induced by task performance, it continued to be present at a uniformly high level between 3 and 12 weeks in the trabeculae, fibrous and cellular periosteum, osteoblasts and osteocytes. In general, the data suggest that PLF is located in tissues during the early adaptive stage of remodeling but not during the pathological phase and therefore might be a marker of early adaptive remodeling.
与工作相关的肌肉骨骼疾病（WMSDs），也被称为过度使用损伤，在美国的工伤和工人赔偿索赔中占相当大的比例。然而，WMSDs潜在的病理生理机制尚未完全了解，尤其是其发展过程中的早期事件。在本研究中，我们使用了上肢WMSD的动物模型，其中大鼠为了获得食物奖励而进行自愿重复性伸展和牵拉任务。这个创新模型为我们提供了一个机会，来研究那些可能用作这些疾病早期诊断标志物和/或未来可作为治疗靶点的分子的作用。本研究检测了骨膜素样因子（PLF）和骨膜素。它们都属于维生素K依赖的γ羧化蛋白家族，其特征是存在保守的成束蛋白结构域，并且除了在慢性超负荷、损伤、应激或病理状态下，在成年组织中未被检测到。通过免疫组织化学和蛋白质印迹分析，检测了执行高重复、高强度任务长达12周的动物以及对照组动物的桡骨和尺骨中PLF和骨膜素定位的时空模式。我们发现，在所有检测的远端骨部位，第3周和第6周时PLF主要存在于细胞性骨膜、关节软骨、成骨细胞、骨细胞和破骨细胞中。这种增加与第6周时血清骨钙素的短暂增加同时出现，表明此时有适应性骨形成。到第12周时，PLF在远端骨膜和干骺端的免疫表达下降，这在时间上与血清抗酒石酸酸性磷酸酶5b（Trap5b）增加、生长板变薄和皮质厚度降低相一致。与PLF不同，一旦骨膜素因任务执行而被诱导，它在第3至12周期间在小梁、纤维性和细胞性骨膜、成骨细胞和骨细胞中持续以均匀的高水平存在。总体而言，数据表明PLF在重塑的早期适应性阶段位于组织中，但在病理阶段则不然，因此可能是早期适应性重塑的标志物。
