Further examining localization, we found that CD68 has a MK-1775 Wee1 inhibitor dome-like distribution in osteoclasts cultured on bone slices. This pattern arises from a concentration of CD68 along the Z-axis of the osteoclast periphery with a more exclusively apical distribution elsewhere. In order to examine the significance of CD68 expression in osteoclasts specifically and the consequences of its ablation in whole animals in general, we used targeted genomic recombination to generate mice that lack expression of CD68. We found that CD682/2 pups appear near expected Mendelian frequencies and have no obvious physical or behavior abnormalities. Analysis of the distal femurs of six-month-old female mice revealed that knockout of CD68 resulted in increased trabecular bone that, nevertheless, has a reduced TMD. The mineral apposition rate of the knockout mice was increased, and this may relate to the observed decrease in trabecular TMD. Rapid bone formation could lead to insufficient mineralization, and there are examples of this in the literature . We also found that CD682/2 osteoclasts differentiated in vitro demonstrated aberrant morphology including accumulation of abnormal intracellular vesicles and increased sensitivity to detachment forces. In addition, osteoclasts that lack CD68 expression showed reduced bone resorption in vitro. These in vitro abnormalities along with histological TRAP staining of femur sections suggest that the increases in trabecular bone in vivo are due to decreased osteoclast activity, not number. A decrease in bone resorption with an increase in bone formation is unusual, as these processes are often paired. There are, however, instances where non-resorbing osteoclast can stimulate osteoblast activity . If this is the case for CD68 knockout mice, CD68 may prove to be a valuable target for an antiresorptive NVP-BEZ235 PI3K inhibitor therapy that uncouples bone formation from bone resorption. The decreased trabecular TMD that results from the increase in MAR is a concern, and the biomechanical properties of bones from CD68 knockout animals should be assessed to determine any consequences of this reduction in TMD. The in vitro phenotype of CD682/2 osteoclasts is intriguing in that it recapitulates many of the abnormalities observed when the vesicular trafficking of osteoclasts is perturbed.