Megakaryocyte-matrix interaction within bone marrow: new roles for fibronectin and factor XIII-A.
The mechanisms by which megakaryocytes (MKs) differentiate and release platelets into the circulation are not well understood. However, growing evidence indicates that a complex regulatory mechanism involving MK-matrix interactions may contribute to the quiescent or permissive microenvironment related to platelet release within bone marrow. To address this hypothesis, in this study we demonstrate that human MKs express and synthesize cellular fibronectin (cFN) and transglutaminase factor XIII-A (FXIII-A). We proposed that these 2 molecules are involved in a new regulatory mechanism of MK-type I collagen interaction in the osteoblastic niche. In particular, we demonstrate that MK adhesion to type I collagen promotes MK spreading and inhibits pro-platelet formation through the release and relocation to the plasma membrane of cFN. This regulatory mechanism is dependent on the engagement of FN receptors at the MK plasma membrane and on transglutaminase FXIII-A activity. Consistently, the same mechanism regulated the assembly of plasma FN (pFN) by adherent MKs to type I collagen. In conclusion, our data extend the knowledge of the mechanisms that regulate MK-matrix interactions within the bone marrow environment and could serve as an important step for inquiring into the origins of diseases such as myelofibrosis and congenital thrombocytopenias that are still poorly understood.
Department of Biochemistry, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Matteo Foundation, University of Pavia, Pavia, Italy.
Alessandro
A
Malara
Cristian
C
Gruppi
Paola
P
Rebuzzini
Livia
L
Visai
Cesare
C
Perotti
Remigio
R
Moratti
Cesare
C
Balduini
Maria Enrica
ME
Tira
Alessandra
A
Balduini
D001792:Blood Platelets / Q000166:cytology; D001853:Bone Marrow; D002448:Cell Adhesion; D048430:Cell Shape; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D026122:Factor XIIIa / Q000096:biosynthesis / Q000502:physiology*; D005353:Fibronectins / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology* / Q000378:metabolism
D024042:Collagen Type I; D005353:Fibronectins; D026122:Factor XIIIa