Mechanical loading prevents the stimulating effect of IL-1 beta on osteocyte-modulated osteoclastogenesis

作者：Kulkarni Rishikesh N; Bakker Astrid D; Everts Vincent; Klein Nulend Jenneke^*

来源：Biochemical and Biophysical Research Communications, 2012, 420(1): 11-16.

DOI：10.1016/j.bbrc.2012.02.099

• Interleukin-1 beta
• Osteocytes
• Osteoclastogenesis
• Mechanical loading
• Pulsating fluid flow

Inflammatory diseases such as rheumatoid arthritis are often accompanied by higher plasma and synovial fluid levels of interleukin-1 beta (IL-1 beta), and by increased bone resorption. Since osteocytes are known to regulate bone resorption in response to changes in mechanical stimuli, we investigated whether IL-1 beta affects osteocyte-modulated osteoclastogenesis in the presence or absence of mechanical loading of osteocytes. %26lt;br%26gt;MLO-Y4 osteocytes were pre-incubated with IL-1 beta (0.1-1 ng/ml) for 24 h. Cells were either or not subjected to mechanical loading by 1 h pulsating fluid flow (PFF: 0.7 +/- 0.3 Pa, 5 Hz) in the presence of IL-1 beta (0.1-1 ng/ml). Conditioned medium was collected after 1 h PFF or static cultures. Subsequently mouse bone marrow cells were seeded on top of the IL-1 beta-treated osteocytes to determine osteoclastogenesis. Conditioned medium from mechanically loaded or static IL-1 beta-treated osteocytes was added to co-cultures of untreated osteocytes and mouse bone marrow cells. Gene expression of cysteine-rich protein 61 (CYR61/CCN1), receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin (OPG) by osteocytes was determined immediately after PFF. %26lt;br%26gt;Incubation of osteocytes with IL-1 beta, as well as conditioned medium from static 1L-1 beta-treated osteocytes increased the formation of osteoclasts. However, conditioned medium from mechanically loaded IL-1 beta-treated osteocytes prevented osteoclast formation. Incubation with IL-1 beta upregulated RANKL and down-regulated OPG gene expression by static osteocytes. PFF upregulated CYR61, RANKL, and OPG gene expression by osteocytes. %26lt;br%26gt;Our results suggest that IL-1 beta increases osteocyte-modulated osteoclastogenesis, and that mechanical loading of osteocytes may abolish IL-1 beta-induced osteoclastogenesis.

• 出版日期2012-3-30