title: Immature and mature megakaryocytes enhance osteoblast proliferation and inhibit osteoclast formation.
abstract: Recent data suggest that megakaryocytes (MKs) play a role in skeletal homeostasis. In vitro and in vivo data show that MKs stimulate osteoblast (OB) proliferation and inhibit osteoclast (OC) formation, thus favoring net bone deposition. There are several mouse models with dysregulated megakaryopoiesis and resultant high bone mass phenotypes. One such model that our group has extensively studied is GATA-1 deficient mice. GATA-1 is a transcription factor required for normal megakaryopoiesis, and mice deficient in GATA-1 have increases in immature MK number and a striking increase in bone mass. While the increased bone mass could simply be a result of increased MK number, here we take a more in depth look at the MKs of these mice to see if there is a unique factor inherent to GATA-1 deficient MKs that favors increased bone deposition. We show that increased MK number does correspond with increased OB proliferation and decreased OC formation that stage of maturation does not alter the effect of MKs on bone cell lineages beyond the megakaryoblast stage, and that GATA-1 deficient MKs survive longer than wild-type controls. So while increased MK number in GATA-1 deficient mice likely contributes to the high bone mass phenotype, we propose that the increased longevity of this lineage also plays a role. Since GATA-1 deficient MKs live longer they are able to exert both more proliferative influence on OBs and more inhibitory influence on OCs.
authors.affiliation: Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Ciovacco
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Cheng
authors.forename: Mark C
authors.initials: MC
authors.lastname: Horowitz
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Kacena
mesh_terms: D000818:Animals; D015519:Bone Density; D001842:Bone and Bones / Q000166:cytology; D019070:Cell Lineage; D049109:Cell Proliferation; D050982:GATA1 Transcription Factor / Q000172:deficiency; D008533:Megakaryocytes / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology*; D010010:Osteoclasts / Q000166:cytology*
chemical_list: D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse