Identification of dexamethasone-dependent osteoprogenitors in cell populations derived from adult human female bone.
The purpose of this investigation was to establish whether or not dexamethasone (Dex)-dependent osteoprogenitors with sufficient proliferative capacity to form a colony of bone-forming osteoblasts could be identified in cell populations isolated from adult human bone. This question is relevant because of the ongoing controversy regarding the effects of dexamethasone on bone formation in humans, the clearly different effects of dexamethasone on osteoprogenitor differentiation in mouse vs. rat bone cell populations, and the related question of whether observations in either rat or mouse systems are applicable to human systems. To answer the question, we isolated cell populations from distal femoral cancellous bone of 8 female patients with osteoarthritis and quantitated the number of Dex-dependent osteoprogenitors in these populations by counting the number of osteoblastic colonies forming bone (bone nodules) or unmineralized bone matrix (osteoid nodules). Dex increased alkaline phosphatase (AP) content in all populations, induced bone nodule formation in 2 of the 8 populations, and induced formation of AP-positive clusters of cells with osteoblastic morphology in one. Treatment with 1,25-dihydroxyvitamin D3 increased osteocalcin (OC) production in the nodule forming populations, but not in the non-nodule-forming populations. Our results thus establish that Dex-dependent osteoprogenitors with sufficient proliferative capacity to form bone or osteoid nodules are present in cell populations derived from adult human bone. They also show that frozen primary human bone cell populations that have been characterized previously in terms of the number of Dex-dependent osteoprogenitors present can be used to further study the characteristics of such progenitors.
Pei
W
W
Faculty of Dentistry, University of Toronto, 124 Edward street, Ontario MSG 1G6, Canada.
Yoshimine
Y
Y
Heersche
J N M
JN
D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism; D001842:Bone and Bones / Q000166:cytology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008875:Middle Aged; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects; D015675:Osteocalcin / Q000096:biosynthesis; D010012:Osteogenesis; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D015675:Osteocalcin; D003907:Dexamethasone; D000469:Alkaline Phosphatase