Gene expression patterns in bone after 4 days of hind-limb unloading in two inbred strains of mice

Introduction: An improved understanding of the interdependence of transcriptional and genomic control of bone loss is critical for the design of effective and safe countermeasures for osteoporosis in space and on Earth. In an effort to test whether molecular pathways modulating the loss of functional weight bearing are dependent on genetic makeup, we quantified the differential expression of genes critical to the early stages of bone remodeling in two different strains of mice. Methods: Adult (4-mo-old) female BALB/cByJ (BALB) and C3H/HeJ (C3H) mice, strains with different sensitivities to unloading, were subjected to hind-limb unloading (HLU) or normal cage activities. RNA was extracted from the tibia following 4 d of HLU and expression levels were determined. Results: In the BALB mice, HLU significantly altered transcriptional levels of osterix (-36%), alkaline phosphatase (-36%), osteonectin (-44%), collagen type I (-55%), MMP2 (-36%), osteocalcin (-68%), and osteopontin (+28%). This expression pattern was highly correlated (R² = 0.75) with altered expression levels in the C3H mice, but the magnitude of altered mRNA levels was less than half of those in the BALB mice. These strain-specific changes in gene expression were consistent with the differential changes in bone formation, as determined in a second group of BALB and C3H mice. Discussion and Conclusions: These data indicate that genetics may influence the absolute changes in gene expression of genes during spaceflight, but that the molecular pathways targeted by countermeasures of bone loss may not need to be specific to an individual's genetic makeup.