Joint loading-driven bone formation and signaling pathways predicted from genome-wide expression profiles.
Joint loading is a recently developed loading modality that induces anabolic responses by lateral loads applied to a synovial joint such as an elbow and a knee. The present study extended this loading modality to an ankle and addressed a question: does ankle loading promote bone formation in the tibia? If so, what signaling pathways are involved in the anabolic responses? Using C57BL/6 female mice as a model system, lateral loads of 0.5 N were applied to the ankle at 5 Hz for 3 min/day for 3 consecutive days and load-driven bone formation was evaluated at three tibial cross-sections (the proximal, middle, and distal diaphysis). Furthermore, total RNA was isolated for 3 pairs of microarray experiments as well as quantitative real-time PCR analyses. The histomorphometric results revealed that in all cross-sections ankle loading elevated the cortical area and thickness as well as the calcein-labeled surface. Signaling pathway analysis from microarray-derived whole-genome mRNA expression profiles and quantitative real-time PCR predicted that molecules in phosphoinositide 3-kinase (PI3K), ECM-receptor interactions, TGFbeta signaling, and Wnt signaling were involved in the joint-loading driven responses. Since ankle loading stimulates bone formation throughout the tibia both in the endosteum and the periosteum, it may provide a non-pharmacological approach to effectively activate molecular signaling necessary for preventing bone loss.
Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA.
Ping
P
Zhang
Charles H
CH
Turner
Hiroki
H
Yokota
D000818:Animals; D001696:Biomechanical Phenomena; D005260:Female; D007596:Joints / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology*; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013314:Stress, Mechanical