INCREASED ADIPOGENESIS AND MYELOPOIESIS IN THE BONE-MARROW OF SAMP6, A MURINE MODEL OF DEFECTIVE OSTEOBLASTOGENESIS AND LOW TURNOVER OSTEOPENIA

Bone formation and hematopoiesis are anatomically juxtaposed and share common regulatory mechanisms, However, little is known about the inte rrelationship between these two processes. We have previously shown th at the senescence accelerated mouse-P6 (SAMP6) exhibits decreased oste oblastogenesis in the bone marrow that is temporally linked with a low rate of bone formation and decreased bone mineral density. Here we re port that in contrast to decreased osteoblastogenesis, ex vivo bone ma rrow cultures from SAMP6 mice exhibited an increase in the number of c olony-forming unit adipocytes, as well as an increase in the number of fully differentiated marrow adipocytes, compared with SAMR1 (nonosteo penic) controls, Further, long-term bone marrow cultures from SAMP6 pr oduced an adherent stromal layer more rapidly, generated significantly more myeloid progenitors and produced more IL-6 and colony-stimulatin g activity, Consistent with this, the number of myeloid cells in fresh ly isolated marrow from SAMP6 mice was increased, as was the number of granulocytes in peripheral blood, The evidence that SAMP6 mice exhibi t decreased osteoblastogenesis, and increased adipogenesis and myelopo iesis, strongly suggests that a switch in the differentiation program of multipotential mesenchymal progenitors may underlie the abnormal ph enotype manifested in the skeleton and other tissues of these animals, Moreover, these observations support the contention for the existence of a reciprocal relationship between osteoblastogenesis and adipogene sis that may explain the association of decreased bone formation and t he resulting osteopenia with the increased adiposity of the marrow see n with advancing age in animals and humans.