Protein-tyrosine phosphatase activity regulates osteoclast formation and function: inhibition by alendronate.

Alendronate (ALN), an aminobisphosphonate used in the treatment of osteoporosis, is a potent inhibitor of bone resorption. Its molecular target is still unknown. This study examines the effects of ALN on the activity of osteoclast protein-tyrosine phosphatase (PTP; protein-tyrosine-phosphate phosphohydrolase, EC 3.1.3.48), called PTPepsilon. Using osteoclast-like cells generated by coculturing mouse bone marrow cells with mouse calvaria osteoblasts, we found by molecular cloning and RNA blot hybridization that PTPepsilon is highly expressed in osteoclastic cells. A purified fusion protein of PTPepsilon expressed in bacteria was inhibited by ALN with an IC50 of 2 microM. Other PTP inhibitors--orthovanadate and phenylarsine oxide (PAO)-inhibited PTPepsilon with IC50 values of 0.3 microM and 18 microM, respectively. ALN and another bisphosphonate, etidronate, also inhibited the activities of other bacterially expressed PTPs such as PTPsigma and CD45 (also called leukocyte common antigen). The PTP inhibitors ALN, orthovanadate, and PAO suppressed in vitro formation of multinucleated osteoclasts from osteoclast precursors and in vitro bone resorption by isolated rat osteoclasts (pit formation) with estimated IC50 values of 10 microM, 3 microM, and 0.05 microM, respectively. These findings suggest that tyrosine phosphatase activity plays an important role in osteoclast formation and function and is a putative molecular target of bisphosphonate action.

Plant genome values: How much do we know?

Plants are the basis of life on earth. We cannot overemphasize their importance. The value of plant genome initiatives is self-evident. The need is to identify priorities for action. The angiosperm genome is highly variable, but the extent of this variability is unknown. Uncertainties remain about the number of genes and the number of species living. Many plants will become extinct before they are discovered. We risk losing both genes and vital information about plant uses. There are also major gaps in our karyotypic knowledge. No chromosome count exists for >70% of angiosperm species. DNA C values are known for only ≈1% of angiosperms, a sample unrepresentative of the global flora. Researchers reported new relationships between genome size and characters of major interest for plant breeding and the environment and the need for more data. In 1997, a Royal Botanic Gardens Kew workshop identified gaps and planned international collaboration to fill them. An electronic version of the Angiosperm DNA C value database also was published. Another initiative, which will make a very significant contribution to the conservation of plant genetic diversity on a global scale is Kew’s Millennium Seed Bank, partly funded by the U.K. Millennium Commission, celebrating the year 2000. Costing up to £80 million (£1 = $1.62), its main aims are to collect and conserve the seed of almost all of the U.K. spermatophyte flora by the year 2000, to collect and conserve a further 10% of the world spermatophyte flora principally from the drylands by 2009, and to provide a world class building as the focus of this activity by 2000.