Potential of resveratrol analogues as antagonists of osteoclasts and promoters of osteoblasts.
The plant phytoalexin resveratrol was previously demonstrated to inhibit the differentiation and bone resorbing activity of osteoclasts, to promote the formation of osteoblasts from mesenchymal precursors in cultures, and inhibit myeloma cell proliferation, when used at high concentrations. In the current study, we screened five structurally modified resveratrol analogues for their ability to modify the differentiation of osteoclasts and osteoblasts and proliferation of myeloma cells. Compared to resveratrol, analogues showed an up to 5,000-fold increased potency to inhibit osteoclast differentiation. To a lesser extent, resveratrol analogues also promoted osteoblast maturation. However, they did not antagonize the proliferation of myeloma cells. The potency of the best-performing candidate in vitro was tested in vivo in an ovariectomy-induced model of osteoporosis, but an effect on bone loss could not be detected. Based on their powerful antiresorptive activity in vitro, resveratrol analogues might be attractive modulators of bone remodeling. However, further studies are required to establish their efficacy in vivo.
Kupisiewicz
Katarzyna
K
Division of Hematology, Department of Clinical Cell Biology, Vejle Hospital, IRS/CSFU, University of Southern Denmark, Vejle, Denmark. kkupisiewicz@health.sdu.dk
Boissy
Patrice
P
Abdallah
Basem M
BM
Hansen
Frederik Dagnaes
FD
Erben
Reinhold G
RG
Savouret
Jean-Francois
JF
Søe
Kent
K
Andersen
Thomas L
TL
Plesner
Torben
T
Delaisse
Jean-Marie
JM
D000818:Animals; D016588:Anticarcinogenic Agents / Q000819:agonists / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000819:agonists / Q000627:therapeutic use; D045744:Cell Line, Tumor; D005260:Female; D006131:Growth Inhibitors / Q000819:agonists* / Q000627:therapeutic use; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D010024:Osteoporosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D000077185:Resveratrol; D013267:Stilbenes / Q000819:agonists* / Q000627:therapeutic use; D016896:Treatment Outcome
D016588:Anticarcinogenic Agents; D050071:Bone Density Conservation Agents; D006131:Growth Inhibitors; D013267:Stilbenes; D000077185:Resveratrol