title: Mitogen-activated protein kinase phosphatase-1: function and regulation in bone and related tissues.
abstract: In this review, we have highlighted work that has clearly demonstrated that mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), a negative regulator of MAPKs, is an important signaling mediator in bone, muscle, and fat tissue homeostasis and differentiation. Further, we examined recent studies with particular focus on MKP-1 overexpression or deletion and its impact on tissues connected to bone. We also summarized regulation of MKP-1 by known skeletal regulators like parathyroid hormone (PTH)/PTH-related peptide (PTHrP) and bone morphogenic proteins. MKP-1's integration into the pathophysiological state of osteoporosis, osteoarthritis, rheumatoid arthritis, obesity, and muscular dystrophy are examined to emphasize possible involvement of MKP-1 both at the molecular level and in disease complications such as sarcopenia- or diabetes-related osteoporosis. We predict that understanding the mechanism of MKP-1-mediated signaling in bone-muscle-fat crosstalk will be a key in coordinating their activities and developing therapeutics to improve clinical outcomes for diseases associated with advanced age.
authors.affiliation: a Division of Endocrinology, Department of Internal Medicine , Wayne State University School of Medicine , Detroit , MI , USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Broome
authors.affiliation: a Division of Endocrinology, Department of Internal Medicine , Wayne State University School of Medicine , Detroit , MI , USA.
authors.forename: Nabanita S
authors.initials: NS
authors.lastname: Datta
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000201:enzymology*; D054638:Dual Specificity Phosphatase 1 / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009928:Organ Specificity; D010011:Osteocytes / Q000201:enzymology; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism
chemical_list: D044162:Parathyroid Hormone-Related Protein; D054638:Dual Specificity Phosphatase 1
keywords: Bone; MAPK phosphatase-1; fat; muscle; pathophysiology; signaling