Melissa A Kacena1, Mark C Horowitz. 1. Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, Connecticut 06520-0871, USA.
Abstract
PURPOSE OF REVIEW: This review provides an update on the role of megakaryocytes in skeletal homeostasis, and discusses these findings in the context of rheumatoid arthritis. RECENT FINDINGS: Thrombocytosis is a common complication of rheumatoid arthritis, and is presumably caused by an up-regulation in megakaryocytopoiesis. In general, patients with rheumatoid arthritis exhibit localized joint bone erosion with systemic bone loss, and rheumatoid arthritis patients with thrombocytosis tend to have more severe disease. Interestingly, in addition to their role in rheumatoid arthritis with thrombocytosis, it has been demonstrated recently that megakaryocytes play a dual role in regulating skeletal mass by inhibiting bone resorption while simultaneously stimulating bone formation. This seeming contradiction in the putative role of megakaryocytes in skeletal regulation and rheumatoid arthritis is the focus of this review. SUMMARY: In rheumatoid arthritis there are substantial increases in the levels of several pro-inflammatory pleiotropic cytokines. As would be expected, in addition to their role in inflammation, these cytokines play a critical role in the megakaryocytopoiesis seen in patients who develop reactive thrombocytosis, and these cytokines also are known to regulate osteoclastogenesis. Thus, it appears that in rheumatoid arthritis with reactive thrombocytosis, the ability of the cytokines to enhance osteoclastogenesis outweighs the ability of megakaryocytes to inhibit osteoclastogenesis.
PURPOSE OF REVIEW: This review provides an update on the role of megakaryocytes in skeletal homeostasis, and discusses these findings in the context of rheumatoid arthritis. RECENT FINDINGS:Thrombocytosis is a common complication of rheumatoid arthritis, and is presumably caused by an up-regulation in megakaryocytopoiesis. In general, patients with rheumatoid arthritis exhibit localized joint bone erosion with systemic bone loss, and rheumatoid arthritispatients with thrombocytosis tend to have more severe disease. Interestingly, in addition to their role in rheumatoid arthritis with thrombocytosis, it has been demonstrated recently that megakaryocytes play a dual role in regulating skeletal mass by inhibiting bone resorption while simultaneously stimulating bone formation. This seeming contradiction in the putative role of megakaryocytes in skeletal regulation and rheumatoid arthritis is the focus of this review. SUMMARY: In rheumatoid arthritis there are substantial increases in the levels of several pro-inflammatory pleiotropic cytokines. As would be expected, in addition to their role in inflammation, these cytokines play a critical role in the megakaryocytopoiesis seen in patients who develop reactive thrombocytosis, and these cytokines also are known to regulate osteoclastogenesis. Thus, it appears that in rheumatoid arthritis with reactive thrombocytosis, the ability of the cytokines to enhance osteoclastogenesis outweighs the ability of megakaryocytes to inhibit osteoclastogenesis.
Authors: Monique Bethel; Calvin L T Barnes; Amanda F Taylor; Ying-Hua Cheng; Brahmananda R Chitteti; Mark C Horowitz; Angela Bruzzaniti; Edward F Srour; Melissa A Kacena Journal: J Cell Physiol Date: 2015-09 Impact factor: 6.384