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Role of PLF in bone remodeling following injury.
Rani-S; Barbe-MF; Barr-AE; Litvin-J
J Bone Miner Res 2007 Sep; 22(S1):S237
Periostin-Like-Factor (PLF) is expressed in developing bone and is up regulated in adult bones that undergo remodeling due to fractures or repeated high force activity which leads to inflammation followed by injury of the bone. PLF over expression by adenovirus in the bone marrow cavity of rats resulted in increased bone formation. Together, these findings suggest that PLF plays an important role in bone formation. To test the hypothesis that PLF promotes bone formation under conditions of remodeling, tissues obtained from the novel model of Upper Extremity-Work-Related Musculoskeletal Disorder (WMSD) in the rat were obtained and subjected to ELISA, immunostaining and Western blot analysis. Twenty two young adult female Sprague Dawley rats were trained to perform a High Repetition High Force (HRHF) voluntary reaching and pulling task, with a food pellet reward. This task entails pulling a lever isometrically at a target rate of 4 reaches/min with 60% max grip force for 2 hrs/day in four 30 min sessions separated by 1.5 hr each, 3days/week and leads to mechanical loading of bone. Loaded bone responds by remodeling and under extreme situations stress fractures and resorptive spaces develop. Tissues from the reach limbs of performing rats and from randomly selected forelimbs of control rats were obtained at various times and subjected to immunostaining and Western blot analysis. To investigate the expression of pro-inflammatory cytokines ELISA assay was done on the bone of performing and control animals. PLF protein was markedly up regulated in the bone of the performing limb of animals exposed to high force and repetitive motion, and the spatial pattern of PLF expression varied over the course of remodeling. Its expression peaked at 6 weeks, during the 12 week-work regimen. It was detected in the periosteum which contains mesenchymal pre-osteoblasts of the ulna and radius, in osteocytes and osteoclasts. It was secreted from proliferating and hypertrophied chondrocytes. The pro-inflammatory cytokines TNF-a and IL-1, also peaked in the bone at 6 weeks of task performance, suggesting a link between the PLF up regulation and the inflammation process. The expression of PLF in bones undergoing remodeling, recovery and repair suggests that PLF plays a significant role in formation and maintenance of bone tissue. Its up regulation concomitant with the presences of high levels of pro-inflammatory mediators also suggests that it has a role in the inflammatory processes. In future experiments the role of PLF in remodeling and inflammation mediated processes will be examined in depth in the WMSD and other fracture repair models.
Animals; Laboratory-animals; Models; Repetitive-work; Musculoskeletal-system; Musculoskeletal-system-disorders; Age-groups; Force; Tissue-culture; Behavior; Bone-structure; Injuries; Proteins
Cooperative Agreement; Grant
Journal of Bone and Mineral Research
PA; HI; DC
Temple University, Philadelphia, Pennsylvania