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Localization of bone morphogenetic proteins (BMPs)-2, -4, and -6 within megakaryocytes and platelets
Joseph B Sipe1, Jianghong Zhang, Chad Waits
1Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Abstract:
In this study, we localized bone morphogenetic proteins (BMPs), proteins known to induce ectopic osteogenesis, within megakaryocytes and in lysates of human platelets. Immunohistochemistry localized BMP-2, -4, and -6 within marrow megakaryocytes of 5-week-old rat tibias. In situ hybridization was utilized to confirm the presence of BMP-2, BMP-4, and BMP-6 mRNA in 2- to 3-week-old mouse tibial marrow megakaryocytes. Finally, the presence of BMP-2, -4, and -6 was confirmed in human platelet lysates using Western blot technique. The expression and release of BMPs by megakaryocytes, within platelets and perhaps by secretion, may help to explain recent reports of excessive bone formation associated with increased numbers of marrow megakaryocytes in GATA-1- or NF-E2 gene-deficient mice. Also, excess local release of BMPs may provide an explanation for the bone overgrowth (osteosclerosis) seen in human patients suffering from a type of myelogenous leukemia characterized by increased numbers of marrow megakaryocytes.
Insights
Bone morphogenetic proteins (BMPs) are found in megakaryocytes and platelets. This discovery may explain excessive bone formation linked to increased megakaryocyte numbers in certain conditions.
Area of Science:
- Biochemistry
- Cell Biology
- Hematology
Background:
- Bone morphogenetic proteins (BMPs) are known to induce ectopic osteogenesis.
- Megakaryocytes are the cells responsible for producing platelets.
- Recent studies suggest a link between increased megakaryocyte numbers and excessive bone formation.
Purpose of the Study:
- To investigate the presence and localization of BMPs within megakaryocytes and human platelets.
- To explore the potential role of megakaryocyte-derived BMPs in bone formation.
Main Methods:
- Immunohistochemistry was used to localize BMP-2, -4, and -6 in rat tibial marrow megakaryocytes.
- In situ hybridization confirmed the presence of BMP mRNA in mouse tibial marrow megakaryocytes.
- Western blot analysis detected BMP-2, -4, and -6 in human platelet lysates.
Main Results:
- BMP-2, -4, and -6 were localized within rat marrow megakaryocytes.
- BMP-2, BMP-4, and BMP-6 mRNA were detected in mouse marrow megakaryocytes.
- BMP-2, -4, and -6 were confirmed in human platelet lysates.
Conclusions:
- Megakaryocytes express and potentially release BMPs, which are stored within platelets.
- This finding may explain excessive bone formation observed in conditions with increased megakaryocyte populations, such as GATA-1 or NF-E2 gene-deficient mice.
- The local release of BMPs by megakaryocytes could also account for osteosclerosis in myelogenous leukemia patients with elevated megakaryocyte counts.
