An osteoclastic protein-tyrosine phosphatase may play a role in differentiation and activity of human monocytic U-937 cell-derived, osteoclast-like cells.
This study investigated if an osteoclastic protein-tyrosine phosphatase (PTP), PTP-oc, plays a role in the functional activity and differentiation of osteoclastic cells by determining the effects of overexpression of wild-type (WT)- or phosphatase-deficient (PD)-PTP-oc on bone resorption activity and differentiation of human promyelomonocytic U-937 cells, which could be induced to differentiate into "osteoclast-like" cells by phorbol ester/1,25(OH)(2)D(3) treatment. U-937 cells overexpressing WT- or PD-PTP-oc were produced with a transposon-based vector. The size and depth of resorption pits created by WT-PTP-oc-overexpressing osteoclast-like cells were greater, while those by PD-PTP-oc-overexpressing osteoclast-like cells were less, than those created by control osteoclast-like cells. Overexpression of WT-PTP-oc also enhanced, while overexpression of PD-PTP-oc suppressed, their differentiation into osteoclast-like cells. Overexpression of WT-PTP-oc increased apoptosis and proliferation of U-937 cells, and overexpression of PD-PTP-oc reduced cell proliferation. Cells overexpressing WT-PTP-oc has also led to greater c-Src and NF-kappabeta activation, whereas cells overexpressing PD-PTP-oc resulted in less c-Src and NF-kappabeta activation. c-Src activation and NF-kappabeta activation each correlated with resorption activity and differentiation into osteoclast-like cells. In summary, these results show that 1) PTP-oc regulates both the activity and the differentiation of osteoclast-like cells derived from U-937 cells; 2) PTP-oc enzymatic activity is important to these processes; 3) high PTP-oc enzymatic activity caused an increase in U-937 cell apoptosis and proliferation, leading to no significant changes in the number of viable cells; and 4) some of the PTP-oc actions are mediated in part by the c-Src and/or NF-kappabeta pathways.
Amoui
Mehran
M
Musculoskeletal Disease Center, Jerry L. Pettis Memorial VA Medical Center, 11201 Benton St., Loma Linda, CA 92357, USA.
Suhr
Sung-Min
SM
Baylink
David J
DJ
Lau
K-H William
KH
D017209:Apoptosis / Q000502:physiology; D000081247:CSK Tyrosine-Protein Kinase; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology*; D006801:Humans; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010010:Osteoclasts / Q000201:enzymology*; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology; D020298:U937 Cells; D019061:src-Family Kinases
D016328:NF-kappa B; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; D017027:Protein Tyrosine Phosphatases