title: Low doses and high doses of heparin have different effects on osteoblast-like Saos-2 cells in vitro.
abstract: Long-term treatment with heparin has been associated with an increased risk of osteoporosis. Given the importance of heparan sulfate proteoglycans for bone metabolism, it can be anticipated that heparin due to its structural similarity with heparan sulfate chains somehow interferes with the biological activities of these cell surface- and extracellular matrix-associated molecules. Initially in order to study the effect(s) of heparin on osteoblasts that possibly contribute to the development of heparin-induced osteoporosis, we treated osteoblast-like Saos-2 cells in monolayer culture for different periods of time with different concentrations of heparin. None of the heparin concentrations tested led to an inhibition of osteoblast proliferation during the early proliferative phase. After longer incubation times, however, cultures treated with higher concentrations of heparin (>/=5 microg/ml) exhibited a reduction in cell number as well as an inhibition of matrix deposition and mineralization. These effects could not be observed with lower heparin concentrations. On the contrary, low concentrations of heparin (5-500 ng/ml) even promoted matrix deposition and its subsequent mineralization. Apparently, heparin has a biphasic effect on osteoblast-like Saos-2 cells, being inhibitory at high concentrations but stimulatory at low concentrations. These results imply that heparin at concentrations well below those used for antithrombotic therapy might eventually turn out to be beneficial for bone formation.
authors.affiliation: University of Ulm, Division for Biochemistry of Joint and Connective Tissue Diseases, Ulm, Germany. heinz-juergen.hausser@medizin.uni-ulm.de
authors.forename: Heinz-Juergen
authors.initials: HJ
authors.lastname: Hausser
authors.forename: Rolf E
authors.initials: RE
authors.lastname: Brenner
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000880:Anthraquinones / Q000737:chemistry; D002113:Calcification, Physiologic / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D005109:Extracellular Matrix / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D005994:Glycerophosphates / Q000494:pharmacology; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000880:Anthraquinones; D005994:Glycerophosphates; D015675:Osteocalcin; C004468:Alizarin Red S; D006493:Heparin; D000469:Alkaline Phosphatase; C031463:beta-glycerophosphoric acid