Reciprocal control of osteoblast/chondroblast and osteoblast/adipocyte differentiation of multipotential clonal human marrow stromal F/STRO-1(+) cells

The regulation of human bone marrow stromal precursor cell differentiation toward the chondrocyte, osteoblast or adipocyte lineages is not known. In t his study, we assessed the lineage-specific differentiation and conversion of immortalized clonal F/STRO-1(+) A human fetal bone marrow stromal cells under the control of dexamethasone (Dex), indomethacin/insulin (Indo/Ins) a nd linoleic acid (LA). Under basal conditions, F/STRO-1+ A cells expressed markers mRNAs or proteins of the osteoblast lineage [CBFA1, osteocalcin (OC ), alkaline phosphatase (ALP), type 1 collagen], of the chondrocyte lineage (aggrecan, types 2, 9 and 10 collagen), and of the adipocyte lineage (PPAR gamma2, C/EBP alpha, aP2, G3PDH, lipoprotein lipase, leptin). Treatment wi th Dex increased CBFA1, OC and ALP mRNA and protein levels. Exposure to LA enhanced expression of adipocytic genes and cytoplasmic triglycerides accum ulation, and suppressed the Dex-induced stimulation of osteoblast marker ge nes. Indo/Ins stimulated the synthesis of aggrecan and type 2 collagen and increased types 9 and 10 collagen mRNA levels, and suppressed both basal an d Dex-promoted expression of osteoblast markers. Conversely, stimulation of osteoblastogenesis by Dex suppressed both basal and Indo/Ins-stimulated ch ondrocyte genes. Thus, the clonal human fetal bone marrow stromal F/STRO-1( +) A cell line is a lineage-unrestricted common progenitor that expresses t ripotential adipocyte, osteoblast or chondrocyte characteristics. Our data also show that differentiation towards one pathway in response to Dex, Indo /Ins and LA restricts expression of other lineage-specific genes, and provi de evidence for a controlled reciprocal regulation of osteoblast/chondrobla st and osteoblast/adipocyte differentiation of clonal F/STRO-1(+) human hon e marrow stromal cells. (C) 2001 Wiley-Liss, Inc.