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Bone mineralization and inflammation genes increase in muscles as a consequence of age and performance of a high repetition task.

Barbe-MF; Safdi-FF; Popoff-SN; Amin-M; Harris-M; Barr-AE
J Bone Miner Res 2006 Sep; 21(S1):S370
We have shown that performance of highly repetitive tasks is associated with increased serum levels of IL-1alpha and increased activated macrophages in musculoskeletal tissues. Our purpose was to examine expression patterns of genes related to bone mineralization and inflammation in flexor forelimb muscles from young adult and aged (16 months) rats performing a repetitive reaching and grasping task. Twelve young adult and 12 aged female Sprague-Dawley rats were used. Six of each age group performed a high repetition low force (HRLF) task for 2 hrs/dy, 3 dys/wk for 3 weeks. The remaining were age-matched controls. Half of the rats were perfused with paraformaldehyde for immunohistochemistry while tissues from the remaining were collected unfixed and flash frozen for molecular analyses. mRNA was extracted using TRizol, Affymetrix oligonucleotide 230A genechip analysis performed and analyzed statistically (3-4/group). A significant upregulation of Osteoactivin, a gene related to bone mineralization, was found in aged rats (both control and task), while alpha-2-HS-glycoprotein was significantly down-regulated in young adult 3 week HRLF task rats only. Clear trends of upregulation of other genes related to bone mineralization were seen as a consequence of 1) age (matrix Gla protein and ameloblastin); 2) both age and task performance (osteopontin); and 3) task performance in aged rats only (soluble fibroblast growth factor receptor IIIb, osteoregulin, and osteocalcin). Significant upregulation of genes related to inflammation were also seen as a consequence of 1) age (interleukin 6 signal transducer, toll protein, complement component 5 receptor 1); 2) task performance in young rats only (attractin, CD59 antigen, complement component factor h); and 3) task performance in aged rats only (corticotropin releasing hormone, interleukin 4, interferon regulatory factor 1, inhibin alpha, and interleukin 6). Also, CD4 antigen, IL-4 and IL-10 mRNA decreased in young 3 week HRLF rats, but not in aged HRLF rats. In contrast, IL-4 was significantly increased in aged 3 week HRLF rats. Microarray results were verified using immunohistochemistry and ELISA for osteoactivin and several interleukins. These results show that a high repetition-low force reaching and grasping task induces genes related to both inflammation and bone mineralization in muscle tissues, suggesting that these molecules play a role in either inflammation or injury healing. Some of these genes are increased as a consequence of age.
Animals; Laboratory-animals; Models; Repetitive-work; Musculoskeletal-system; Musculoskeletal-system-disorders; Age-groups; Force; Tissue-culture; Behavior; Bone-structure; Injuries; Genes; Muscles; Cumulative-trauma; Cumulative-trauma-disorders
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Cooperative Agreement
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Journal of Bone and Mineral Research
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Temple University, Philadelphia, Pennsylvania