| The balance between bone formation and bone resorption involves the coordinated activities of osteoblasts and osteoclasts. Communication between these two cell types is essential for maintenance of normal bone homeostasis; however, the mechanisms by which this cross talk is regulated are not completely understood. Identifying factors that regulate both osteoblast and osteoclast differentiation and function is an important step in elucidating these regulatory pathways. Recently we have demonstrated that the LIM protein LIMD1 affects stress osteoclastogenesis in vivo. One possible mechanism explaining this defect is that Limd1 affects osteoclastogenesis through modulation of osteoblast development and function.;In order to test this hypothesis, I analyzed osteoblast differentiation and function in primary calvarial osteoblasts isolated from Limd1 -/- or wt mice. In addition, Limd1-/- and wt mice were compared at steady state or in response to sustained or acute parathyroid hormone stimulus by DEXA, micro-CT and histomorphometry analyses. Finally, the number of mesenchymal-derived osteoblast progenitors in Limd1-/- and wt mice was determined and compared.;Defects in both differentiation and function of primary calvarial cells in culture were found. Limd1-/- calvarial cells display increased mineralization and support less osteoclastogenesis than wt calvarial cells. Analysis of gene profiles during osteoblast differentiation suggested that Limd1-/- calvarial cells adopt a mature osteoblast phenotype sooner than wt controls. This accelerated differentiation may contribute to the decreased stress osteoclastogenesis observed in vivo. Although Limd1-/- mice lack any gross skeletal abnormalities at steady state, they exhibited an initial increase in bone density in response to sustained PTH treatment and enhanced bone formation rates in response to acute PTH treatment. Intriguingly, Limd1-/- mice contained significantly more osteoblast progenitors than wt mice. Furthermore, Limd1-/- osteoblast progenitors differentiated faster than wt controls. Together, these results demonstrated that Limd1 influences normal osteoblast function and osteoblast progenitor commitment. Therefore, we have identified Limd1 as a novel regulator of osteoblast development. |
