Abstract
Mechanical disuse will bias bone marrow stromal cells towards adipogenesis, ultimately compromising the regenerative capacity of the stem cell pool and impeding the rapid and full recovery of bone morphology. Here, it was tested whether brief daily exposure to high-frequency, low-magnitude vibrations can preserve the marrow environment during disuse and enhance the initiation of tissue recovery upon reambulation. Male C57BL/6J mice were subjected to hindlimb unloading (HU, n = 24), HU interrupted by weight-bearing for 15 min/d (HU+SHAM, n = 24), HU interrupted by low-level whole body vibrations (0.2 g, 90 Hz) for 15 min/d (HU+VIB, n = 24), or served as age-matched controls (AC, n = 24). Following 3 w of disuse, half of the mice in each group were released for 3 w of reambulation (RA), while the others were sacrificed. RA+VIB mice continued to receive vibrations for 15 min/d while RA+SHAM continued to receive sham loading. After disuse, HU+VIB mice had a 30% greater osteogenic marrow stromal cell population, 30% smaller osteoclast surface, 76% greater osteoblast surface but similar trabecular bone volume fraction compared to HU. After 3 w of reambulation, trabecular bone of RA+VIB mice had a 30% greater bone volume fraction, 51% greater marrow osteoprogenitor population, 83% greater osteoblast surfaces, 59% greater bone formation rates, and a 235% greater ratio of bone lining osteoblasts to marrow adipocytes than RA mice. A subsequent experiment indicated that receiving the mechanical intervention only during disuse, rather than only during reambulation, was more effective in altering trabecular morphology. These data indicate that the osteogenic potential of bone marrow cells is retained by low-magnitude vibrations during disuse, an attribute which may have contributed to an enhanced recovery of bone morphology during reambulation.
Highlights
The removal of weight-bearing from the skeleton as a consequence of spaceflight, bedrest, paraplegia, or aging adversely affects the mass and architecture of trabecular bone [1,2]
Failure of the bone structure to recover on reambulation may in part be caused by the collapse of the osteogenic potential of bone marrow cell populations during disuse
Consistent with the importance of mechanical signals to maintain the osteogenic potential of bone marrow cells, superposition of exogenous mechanical signals onto normal daily activities can enhance bone at both the cellular and tissue levels [9,10,11] with exercise promoting osteoblastogenesis and inhibiting adipogenesis [12]
Summary
The removal of weight-bearing from the skeleton as a consequence of spaceflight, bedrest, paraplegia, or aging adversely affects the mass and architecture of trabecular bone [1,2]. Failure of the bone structure to recover on reambulation may in part be caused by the collapse of the osteogenic potential of bone marrow cell populations during disuse. A reduced or distracted niche of osteogenic cells may not be capable to effectively rebuild the intricate skeletal morphology upon the reintroduction of regulatory signals associated with load-bearing [8]. Consistent with the importance of mechanical signals to maintain the osteogenic potential of bone marrow cells, superposition of exogenous mechanical signals onto normal daily activities can enhance bone at both the cellular and tissue levels [9,10,11] with exercise promoting osteoblastogenesis and inhibiting adipogenesis [12]. Despite the various benefits that exercise provides, many exercise-based interventions have been ineffective in stemming tissue deterioration during disuse [1,13,14] or to fully recapture bone mass upon reambulation [1,15]
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