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Megakaryocytes contribute to the bone marrow-matrix environment by expressing fibronectin, type IV collagen, and laminin.

ABSTRACT: Megakaryocytes associate with the bone marrow vasculature where they convert their cytoplasm into proplatelets that protrude through the vascular endothelium into the lumen and release platelets. The extracellular matrix (ECM) microenvironment plays a critical role in regulating these processes. In this work we demonstrate that, among bone marrow ECM components, fibronectin, type IV collagen, and laminin are the most abundant around bone marrow sinusoids and constitute a pericellular matrix surrounding megakaryocytes. Most importantly, we report, for the first time, that megakaryocytes express components of the basement membrane and that these molecules contribute to the regulation of megakaryocyte development and bone marrow ECM homeostasis both in vitro and in vivo. In vitro, fibronectin induced a threefold increase in the proliferation rate of mouse hematopoietic stem cells leading to higher megakaryocyte output with respect to cells treated only with thrombopoietin or other matrices. However, megakaryocyte ploidy level in fibronectin-treated cultures was significantly reduced. Stimulation with type IV collagen resulted in a 1.4-fold increase in megakaryocyte output, while all tested matrices supported proplatelet formation to a similar extent in megakaryocytes derived from fetal liver progenitor cells. In vivo, megakaryocyte expression of fibronectin and basement membrane components was upregulated during bone marrow reconstitution upon 5-fluorouracil induced myelosuppression, while only type IV collagen resulted upregulated upon induced thrombocytopenia. In conclusion, this work demonstrates that ECM components impact megakaryocyte behavior differently during their differentiation and highlights a new role for megakaryocyte as ECM-producing cells for the establishment of cell niches during bone marrow regeneration.

SUBMITTER: Malara A

PROVIDER: S-EPMC4096110 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Megakaryocytes contribute to the bone marrow-matrix environment by expressing fibronectin, type IV collagen, and laminin.

Malara Alessandro A Currao Manuela M Gruppi Cristian C Celesti Giuseppe G Viarengo Gianluca G Buracchi Chiara C Laghi Luigi L Kaplan David L DL Balduini Alessandra A

Stem cells (Dayton, Ohio) 20140401 4

Megakaryocytes associate with the bone marrow vasculature where they convert their cytoplasm into proplatelets that protrude through the vascular endothelium into the lumen and release platelets. The extracellular matrix (ECM) microenvironment plays a critical role in regulating these processes. In this work we demonstrate that, among bone marrow ECM components, fibronectin, type IV collagen, and laminin are the most abundant around bone marrow sinusoids and constitute a pericellular matrix surr ...[more]

PMID: 24357118

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Project description:Introduction: It is important to note that complete myelination and formation of myelinated fibers are essential for functional nerve regeneration after peripheral nerve injury (PNI). However, suboptimal myelin regeneration is common and can hinder ideal nerve regeneration. Therefore, it is important to closely monitor and support myelin regeneration in patients with PNI to achieve optimal outcomes. Methods: This study analyzed the effects of three extracellular matrix (ECM) proteins on Schwann cells (SCs) in the nerve regeneration environment, including their adhesion, proliferation, and migration. The study also explored the use of composite sodium alginate hydrogel neural scaffolds with ECM components and investigated the effects of ECM proteins on remyelination following peripheral nerve injury. Results: The results showed that laminin (LN), fibronectin (FN), and collagen Ⅳ (type IV Col) promoted the early adhesion of SCs in 2-dimensional culture but the ratios of early cell adhesion were quite different and the maintenance of cells’ morphology by different ECM proteins were significantly different. In transwell experiment, the ability of LN and FN to induce the migration of SCs was obviously higher than that of type IV Col. An vitro co-culture model of SCs and dorsal root ganglia (DRG) neurons showed that LN promoted the transition of SCs to a myelinated state and the maturation of the myelin sheath, and increased the thickness of neurofilaments. Animal experiments showed that LN had superior effects in promoting myelin sheath formation, axon repair, and reaching an ideal G-ratio after injury compared to FN and Col IV. The situation of gastrocnemius atrophy was significantly better in the LN group. Notably, the thickness of the regenerated myelin sheaths in the type IV Col group was the thickest. Conclusion: In this experiment, we analyzed and compared the effects of LN, FN, and type IV Col on the biological behavior of SCs and their effects on remyelination after PNI and further clarified their unique roles in the process of remyelination. Further research is necessary to explore the underlying mechanisms.

Dataset Information

Megakaryocytes contribute to the bone marrow-matrix environment by expressing fibronectin, type IV collagen, and laminin.

Publications

Megakaryocytes contribute to the bone marrow-matrix environment by expressing fibronectin, type IV collagen, and laminin.

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