ARS | Publication request: Feeding Blueberry Diets in Early Life Prevent Senescence of Osteoblasts and Bone Loss in Ovariectomized Adult Female Rats

Submitted to: PLoS One
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 11, 2011
Publication Date: September 6, 2011
Citation: Zhang, J., Lazarenko, O.P., Blackburn, M.L., Shankar, K., Badger, T.M., Ronis, M.J., Chen, J. 2011. Feeding Blueberry Diets in Early Life Prevent Senescence of Osteoblasts and Bone Loss in Ovariectomized Adult Female Rats. PLoS One. 6(9):e24486. doi:10.1371/journal.pone.0024486.

Interpretive Summary: Appropriate nutrition during early development is essential for optimal bone formation; however, linkage between early life nutrition, childhood bone mass and prevention of bone loss later in life has not been extensively studied. In this report, we show that feeding a high quality diet supplemented with blueberries (BB), to rapidly growing rats throughout experiment or only between postnatal day 20 (PND20), and PND34 prevented ovariectomy (OVX)-induced bone loss in adult life. This protective effect of BB is due to suppression of bone forming cell, osteoblastic cell from entering un-expected aging. Mechanistically, in female rats, after sex steroid acutely decreasing, cellular organism of bone forming cell became dis-organized and BB diet protected it. These results indicate: 1) a significant prevention of OVX-induced bone loss in adult rats can occur with only 14 days consumption of a BB-containing diet immediately prior to puberty; and 2) the molecular mechanisms underlying these effects involves increased myosin production which stimulates osteoblast differentiation and reduces mesenchymal stromal cell senescence.

Technical Abstract: Appropriate nutrition during early development is essential for optimal bone mass accretion; however, linkage between early nutrition, childhood bone mass and prevention of bone loss later in life has not been extensively studied. In this report, we show that feeding a high quality diet supplemented with blueberries (BB) to pre-pubertal rats throughout development, or only between postnatal day 20 (PND20) and PND34 prevented ovariectomy (OVX)-induced bone loss in adult life. This protective effect of BB is due to suppression of osteoblastic cell senescence, which is associated with acute and profound loss of myosin expression after OVX. Early exposure of pre-osteoblasts to serum from BB-fed rats was found to consistently increase myosin expression. This led to maintenance osteoblastic cell development and differentiation and delay cell entrance into senescence by regulation of the Runx2 gene. High bone turnover after OVX results in insufficient collagenous matrix support for new osteoblasts and their precursors to express myosin and other cytoskeletal elements required for osteoblast activity and differentiation. Co-immuno-precipitation revealed an association between myosin and Runx2 in osteogenic cells and osteoblast precursors, and serum from OVX control rats decreased (P<0.05) this myosin and Runx2 complex. Knockdown of the non-muscular myosin II gene in ST2 cells resulted in reduced expression of Runx2 mRNA, and reduced the potential for cells to differentiate into osteoblasts even in the presence of BB serum. Following treatment with shRNA to myosin, ST2 cells expressed greater (P<0.05) senescence-associated beta-galactosidase activity, indicating increased stromal cell senescence. These results indicate: 1) a significant prevention of OVX-induced bone loss in adult rats can occur with only 14 days consumption of a BB-containing diet immediately prior to puberty; and 2) the molecular mechanisms underlying these effects involves increased myosin production which stimulates osteoblast differentiation and reduces mesenchymal stromal cell senescence.