TY - JOUR
T1 - Serine/threonine phosphatases in osteoclastogenesis and bone resorption
AU - Karkache, Ismael Y.
AU - Damodaran, Jeyaram R.
AU - Molstad, David H.H.
AU - Bradley, Elizabeth W.
N1 - Funding Information:
The authors have no competing interests to declare. This work was made possible by a research grant from the National Institutes of Health (AR072634) and the University of Minnesota Board of Regents. These contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2021/3/1
Y1 - 2021/3/1
N2 - Maintenance of optimal bone mass is controlled through the concerted functions of several cell types, including bone resorbing osteoclasts. Osteoclasts function to remove calcified tissue during developmental bone modeling, and degrade bone at sites of damage during bone remodeling. Changes to bone homeostasis can arise with alterations in osteoclastogenesis and/or catabolic activity that are not offset by anabolic activity; thus, factors that regulate osteoclastogenesis and bone resorption are of interest to further our understanding of basic bone biology, and as potential targets for therapeutic intervention. Several key cytokines, including RANKL and M-CSF, as well as co-stimulatory factors elicit kinase signaling cascades that promote osteoclastogenesis. These kinase cascades are offset by the action of protein phosphatases, including members of the serine/threonine phosphatase family. Here we review the functions of serine/threonine phosphatases and their control of osteoclast differentiation and function, while highlighting deficiencies in our understanding of this understudied class of proteins within the field.
AB - Maintenance of optimal bone mass is controlled through the concerted functions of several cell types, including bone resorbing osteoclasts. Osteoclasts function to remove calcified tissue during developmental bone modeling, and degrade bone at sites of damage during bone remodeling. Changes to bone homeostasis can arise with alterations in osteoclastogenesis and/or catabolic activity that are not offset by anabolic activity; thus, factors that regulate osteoclastogenesis and bone resorption are of interest to further our understanding of basic bone biology, and as potential targets for therapeutic intervention. Several key cytokines, including RANKL and M-CSF, as well as co-stimulatory factors elicit kinase signaling cascades that promote osteoclastogenesis. These kinase cascades are offset by the action of protein phosphatases, including members of the serine/threonine phosphatase family. Here we review the functions of serine/threonine phosphatases and their control of osteoclast differentiation and function, while highlighting deficiencies in our understanding of this understudied class of proteins within the field.
KW - Bone remodeling
KW - Kinase
KW - M-CSF
KW - Myeloid lineage
KW - Osteoclast
KW - Phosphatase inhibitor
KW - RANKL
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U2 - 10.1016/j.gene.2020.145362
DO - 10.1016/j.gene.2020.145362
M3 - Review article
C2 - 33338510
AN - SCOPUS:85098963061
SN - 0378-1119
VL - 771
JO - Gene
JF - Gene
M1 - 145362
ER -