The mouse fibula as a suitable bone for the study of functional adaptation to mechanical loading

Abstract

Bones' functionally adaptive responses to mechanical loading can usefully be studied in the tibia by the application of loads between the knee and ankle in normal and genetically modified mice. Such loading also deforms the fibula. Our present study was designed to ascertain whether the fibula adapts to loading in a similar way to the tibia and could thus provide an additional bone in which to study functional adaptation. The right tibiae/fibulae in C57BL/6 mice were subjected to a single period of axial loading (40 cycles at 10 Hz with 10-second intervals between each cycle; approximately 7 min/day, 3 alternate days/week, 2 weeks). The left tibiae/fibulae were used as non-loaded, internal controls. Both left and right fibulae and tibiae were analyzed by micro-computed tomography at the levels of the mid-shaft of the fibula and 25% from its proximal and distal ends. We also investigated the effects of intermittent parathyroid hormone (iPTH) on the (re)modelling response to 2-weeks of loading and the effect of 2-consecutive days of loading on osteocytes' sclerostin expression. These in vivo experiments confirmed that the fibula showed similar loading-related (re)modelling responses to those previously documented in the tibia and similar synergistic increases in osteogenesis between loading and iPTH. The numbers of sclerostin-positive osteocytes at the proximal and middle fibulae were markedly decreased by loading. Collectively, these data suggest that the mouse fibula, as well as the tibia and ulna, is a useful bone in which to assess bone cells' early responses to mechanical loading and the adaptive (re)modelling that this engenders.

The P2Y13 receptor regulates extracellular ATP metabolism and the osteogenic response to mechanical loading

“…The peak load (15N) was selected to induce bone formation in the loaded tibiae because evidence showed that similar peak load can induce osteogenic response in female C57BL/6 mice. (26,29,30) Briefly, a 14.5-N dynamic load was superimposed onto a 0.5-N preload at rate of 160,000 N/second. Forty trapezoidal-waveform load cycles (0.2-second hold at 15 N) with a 10-second interval between each cycle were applied to mice tibiae, three times a week for 2 weeks.…”

Sclerostin: A gem from the genome leads to bone-building antibodies

“…(58) Others have subsequently replicated many of these initial results. (59) In addition to decreased SOST/sclerostin, there also was a loadinginduced significant reduction in another Wnt signaling antagonist, DKK1. Conversely, tail suspension, a rodent model for disuse-induced bone loss, resulted in an increase in SOST mRNA levels in the mouse tibia, suggesting that SOST expression is also modulated by mechanical unloading.…”

Effects of whole-body vibration on plasma sclerostin level in healthy women

“…It has been recently shown that mechanical stimulation of long bones in mice suppresses sclerostin expression in osteocytes and simultaneously induces bone formation in rodents (2,6,7). Conversely, mechanical unloading causes upregulation of sclerostin activity in mice and disuse osteoporosis in humans (1,4).…”