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Structurally different bisphosphonates exert opposing effects on alkaline phosphatase and mineralization in marrow osteoprogenitors
Author(s) -
Klein Benjamin Y.,
BenBassat Hannah,
Breuer Eli,
Solomon Vered,
Golomb Gershon
Publication year - 1998
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19980201)68:2<186::aid-jcb5>3.0.co;2-r
Subject(s) - mineralization (soil science) , alkaline phosphatase , chemistry , bone marrow , cancer research , microbiology and biotechnology , biochemistry , biology , medicine , enzyme , organic chemistry , nitrogen
Abstract Bisphosphonates (BPs) are inhibitors of bone resorption and soft tissue calcification. The biological effects of the BPs in calcium‐related disorders are attributed mainly to their incorporation in bone, enabling direct interaction with osteoclasts and/or osteoblasts through a variety of biochemical pathways. Structural differences account for the considerable differences in the pharmacological activity of BPs. We compared the effects of two structurally different compounds, alendronate and 2‐(3′‐dimethylaminopyrazinio)ethylidene‐1,1‐bisphosphonic acid betaine (VS‐6), in an osteoprogenitor differentiation system. The BPs were examined in a bone marrow stromal‐cell culture system, which normally results in osteoprogenitor differentiation. The drugs were present in the cultures from days 2 to 11 of osteogenic stimulation, a period estimated as being comparable to the end of proliferation and the matrix‐maturation stages. We found that the two different BPs have opposing effects on specific alkaline phosphatase (ALP) activity, on stromal‐cell proliferation, and on cell‐mediated mineralization. These BPs differentially interact with cell‐associated phosphohydrolysis, particularly at a concentration of 10 −2 of ALP K m , in which alendronate inhibits whereas VS‐6 did not inhibit phosphatase activity. VS‐6 treatment resulted in similar and significantly increased mineralization at 10 and 1 μM drug concentrations, respectively. In contrast, mineralization was similar to control, and significantly decreased at 10 and 1 μM drug concentrations, respectively, under alendronate treatment. J. Cell. Biochem. 68:186–194, 1998. © 1998 Wiley‐Liss, Inc.