Weight-bearing bone is constantly adapting its structure and function to mechanical environments. Loading through routine exercises stimulates bone formation and prevents bone loss, but unloading through bed rest and cast immobilization as well as exposure to weightlessness during spaceflight reduces its mass and strength. In order to elucidate the mechanism underlying unloading-driven bone adaptation, ground-based in vitro and in vivo analyses have been conducted using rotating cell culturing and hindlimb suspension. Focusing on gene expression studies in osteoblasts and hindlimb suspension studies, this minireview introduces our recent understanding on bone homeostasis under weightlessness in space. Most of the existing data indicate that unloading has the opposite effects to loading through common signaling pathways. However, a question remains as to whether any pathway unique to unloading (and not to loading) may exist.
Adaptation, Physiological ; Animals ; Bone and Bones ; cytology ; physiology ; Hindlimb Suspension ; physiology ; Humans ; Osteoblasts ; physiology ; Weightlessness

Animals ; Exobiology ; methods ; Extraterrestrial Environment ; Genomics ; Humans ; Space Flight

Understanding the regulatory mechanism that controls the alteration of global gene expression patterns continues to be a challenging task in computational biology. We previously developed an ant algorithm, a biologically-inspired computational technique for microarray data, and predicted putative transcription-factor binding motifs (TFBMs) through mimicking interactive behaviors of natural ants. Here we extended the algorithm into a set of web-based software, Ant Modeler, and applied it to investigate the transcriptional mechanism underlying bone formation. Mechanical loading and administration of bone morphogenic proteins (BMPs) are two known treatments to strengthen bone. We addressed a question: Is there any TFBM that stimulates both "anabolic responses of mechanical loading" and "BMP-mediated osteogenic signaling"? Although there is no significant overlap among genes in the two responses, a comparative model-based analysis suggests that the two independent osteogenic processes employ common TFBMs, such as a stress responsive element and a motif for peroxisome proliferator-activated receptor (PPAR). The post-modeling in vitro analysis using mouse osteoblast cells supported involvements of the predicted TFBMs such as PPAR, Ikaros 3, and LMO2 in response to mechanical loading. Taken together, the results would be useful to derive a set of testable hypotheses and examine the role of specific regulators in complex transcriptional control of bone formation.
Algorithms ; Animals ; Base Sequence ; Binding Sites ; genetics ; Biomechanical Phenomena ; Bone Morphogenetic Proteins ; pharmacology ; Consensus Sequence ; DNA ; genetics ; metabolism ; Databases, Genetic ; Gene Expression Profiling ; statistics & numerical data ; Genomics ; statistics & numerical data ; Mice ; Oligonucleotide Array Sequence Analysis ; statistics & numerical data ; Osteoblasts ; drug effects ; metabolism ; Osteogenesis ; drug effects ; genetics ; physiology ; Transcription Factors ; metabolism