Accelerated Chondrogenesis of the Rabbit Cranial Base Growth Plate by Oscillatory Mechanical Stimuli

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Abstract
How mechanical stimuli modulate chondral growth is not well understood. To test a hypothesis that chondral growth is accelerated by oscillatory mechanical stimuli rather than the peak magnitude of mechanical force, we delivered 2-N tensile forces with static (frequency = 0 Hz) and cyclic (f = 1 Hz) profiles noninvasively to the maxillae of growing New Zealand white rabbits for 20 minutes/day over 12 days. Computerized histomorphometry revealed significantly greater maximum height of the cranial base growth plate (GP) treated with cyclic forces (870 +/- 130 microm) than static forces (654 +/- 29 microm) and sham controls (566 +/- 47 microm). In addition, the average total GP area treated with cyclic forces (2.63 +/- 0.17 mm2) was significantly greater than static forces (2.12 +/- 0.99 mm2) and sham controls (1.65 +/- 0.13 mm2). The proliferating zone of GPs treated with cyclic forces (158 +/- 38.5 microm) was significantly longer than the corresponding zones of static forces (117 +/- 8.6 microm) and sham controls (54 +/- 14.9 microm). The average number of chondrocytes in the proliferating zone treated with cyclic forces (1045 +/- 127) was significantly greater than static forces (632 +/- 85) and sham controls (632 +/- 60) in standardized grids. Like natural GPs, the cartilage matrix treated with cyclic and static tensile forces consisted of abundant aggrecan-like proteoglycans. These findings indicate that oscillatory components of mechanical force rather than its peak magnitude are potent anabolic stimulus for chondral growth. A cascade of oscillatory mechanical stimuli is likely capable of engineering chondral growth beyond naturally occurring chondrogenesis.