title: Lrp5 is not required for the proliferative response of osteoblasts to strain but regulates proliferation and apoptosis in a cell autonomous manner.
abstract: Although Lrp5 is known to be an important contributor to the mechanisms regulating bone mass, its precise role remains unclear. The aim of this study was to establish whether mutations in Lrp5 are associated with differences in the growth and/or apoptosis of osteoblast-like cells and their proliferative response to mechanical strain in vitro. Primary osteoblast-like cells were derived from cortical bone of adult mice lacking functional Lrp5 (Lrp5(-/-)), those heterozygous for the human G171V High Bone Mass (HBM) mutation (LRP5(G171V)) and their WT littermates (WT(Lrp5), WT(HBM)). Osteoblast proliferation over time was significantly higher in cultures of cells from LRP5(G171V) mice compared to their WT(HBM) littermates, and lower in Lrp5(-/-) cells. Cells from female LRP5(G171V) mice grew more rapidly than those from males, whereas cells from female Lrp5(-/-) mice grew more slowly than those from males. Apoptosis induced by serum withdrawal was significantly higher in cultures from Lrp5(-/-) mice than in those from WT(HBM) or LRP5(G171V) mice. Exposure to a single short period of dynamic mechanical strain was associated with a significant increase in cell number but this response was unaffected by genotype which also did not change the 'threshold' at which cells responded to strain. In conclusion, the data presented here suggest that Lrp5 loss and gain of function mutations result in cell-autonomous alterations in osteoblast proliferation and apoptosis but do not alter the proliferative response of osteoblasts to mechanical strain in vitro.
authors.affiliation: Department of Oral Biology, UMKC School of Dentistry, Kansas City, Missouri, United States of America. javaherib@umkc.edu
authors.forename: Behzad
authors.initials: B
authors.lastname: Javaheri
authors.forename: Andrew
authors.initials: A
authors.lastname: Sunters
authors.forename: Gul
authors.initials: G
authors.lastname: Zaman
authors.forename: Rosemary F L
authors.initials: RF
authors.lastname: Suswillo
authors.forename: Leanne K
authors.initials: LK
authors.lastname: Saxon
authors.forename: Lance E
authors.initials: LE
authors.lastname: Lanyon
authors.forename: Joanna S
authors.initials: JS
authors.lastname: Price
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism
chemical_list: D060492:Low Density Lipoprotein Receptor-Related Protein-5; C555483:Lrp5 protein, mouse