HUMAN TRABECULAR BONE-CELLS ARE ABLE TO EXPRESS BOTH OSTEOBLASTIC ANDADIPOCYTIC PHENOTYPE - IMPLICATIONS FOR OSTEOPENIC DISORDERS

The decrease in bone volume associated with osteoporosis and age-relat ed osteopenia is accompanied by increased marrow adipose tissue format ion, Reversal of this process may provide a novel therapeutic approach for osteopenic disorders, We have shown that cells cultured from huma n trabecular bone are not only osteogenic, but are able also to underg o adipocyte differentiation under defined culture conditions, Osteobla st differentiation was induced by 1,25-dihydroxyvitamin D-3 (1,25(OH)( 2)D-3) and adipocyte differentiation by dexamethasone (dex) plus 3-iso butyl-1-methylxanthine (IBMX) treatment, Adipogenesis was characterize d by lineage-specific enzyme and gene activities, alpha-glycerophospha te-3-dehydrogenase activity, fatty acid binding protein, aP2 and lipop rotein lipase expression, Osteoblastogenesis was assessed by osteoblas t characteristic 1,25(OH)(2)D-3 induction of alkaline phosphatase acti vity and osteoblast-specific 1,25(OH)(2)D-3-induced osteocalcin synthe sis and release, We provide evidence for a common pluripotent mesenchy mal stem cell that is able either to undergo adipogenesis or osteoblas togenesis, using clonal cell lines derived from human trabecular bone cell cultures, Adipogenesis can be induced also by long chain fatty ac ids and the thiazolidinedione troglitazone. Dex plus IBMX-induced adip ogenesis can be inhibited by interleukin-1 beta, tumor necrosis factor -alpha, and transforming growth factor-beta, Interestingly, and in con trast to extramedullary adipocyte differentiation as shown by mouse 3T 3L-1 and a human liposarcoma SW872 cell line, trabecular bone adipogen esis was unaffected by insulin, Also, the formation of fully different iated adipocytes from trabecular bone cells after troglitazone treatme nt and long chain fatty acids was dependent on increased expression of the nuclear hormone receptor peroxisome proliferator-activated recept or gamma 2 caused by dex plus IBMX, Specific inhibition of marrow adip ogenesis and promotion of osteoblastogenesis of a common precursor cel l may provide a novel therapeutic approach to the treatment of osteope nic disorders.