Frequency of stromal lineage colony forming units in bone marrow of peroxisome proliferator-activated receptor-alpha-null mice

The bone marrow stroma, consisting of adipocytes, fibroblasts, and osteobla sts, develops from a multipotent mesenchymal progenitor. The recently descr ibed nuclear hormone receptors, known as peroxisome proliferator-activated receptors (PPARs), regulate transcription of genes involved in adipogenesis , Consistent with this is the observation that PPAR alpha-null mice exhibit greater extramedullary adipose stores compared with their wild-type contro ls. To determine if the status of the PPAR alpha protein also influenced bo ne marrow stromal cell differentiation, this study compared the frequency o f colony forming units for bone marrow adipocytes (CFU-A), alkaline phospha tase-positive fibroblasts (CFU-F/ALP(+)), and osteoblasts (CFU-O) between w ild-type and PPARa-null mice. The CFU frequencies for all lineages were not significantly different in either gender at age 3 weeks, independent of th e PPAR alpha background. However, histologic analysis showed that the cross -sectional area of the femur in male PPAR alpha null mice was significantly greater than that of PPAR alpha-null female mice and of both wild-type gen ders. This was due to an increased marrow cavity space rather than an incre ased cortical bone area. In addition, while the percentage area of cortical bone occupied by lacunae was equivalent in the PPAR alpha and wild-type ma les, this value was significantly greater in PPAR alpha-null female mice co mpared with wild-type females, At age 3-6 months, no significant difference was observed in the CFU-A frequencies, based on either PPAR alpha status o r gender. The wild-type male CFU-F/ALP(+) frequency was significantly great er than the CFU-F/ALP(+) in all other groups. Although the PPARa status had no influence on the CFU-O frequency, the number of CFU-O was greater in ma le than in female mice. Sequential incubation of stromal cells in either ad ipogenic- or osteoblastic-inducing media did not alter the number of CFU-A or CFU-O, These results indicate that the PPAR alpha-null genotype does not influence bone marrow stromal cell numbers. (C) 2000 by Elsevier Science I nc. All rights reserved.