Expression of bone morphogenetic proteins and their receptors in the bone marrow megakaryocytes of GATA-1low mice

A possible role in osteosclerosis

Rama Garimella, Melissa Kacena, Sarah E. Tague, Jinxi Wang, Mark C. Horowitz, H. Clarke Anderson

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The mechanism of osteosclerosis associated with myelofibrosis in megakaryocyte (MK)-related myeloproliferative disorders is largely unknown. However, growth factors released from the bone marrow cells, including from MKs, have been implicated in myelofibrosis, osteosclerosis, and angiogenesis. GATA-1 is a transcription factor required for normal MK development. GATA-1 deficiency in mice (GATA-1low) leads to increased megakaryocytic proliferation, followed by osteosclerosis and myelofibrosis. In this study we investigated the expression of bone morphogenetic proteins (BMPs) and BMP receptors and their possible role in the development of osteosclerosis in the MKs of 12-month-old GATA-1low mice by immunohistochemistry, cytomorphometry, and quantitative real-time PCR. Marrow MKs from both wild-type and GATA-1 low mice showed moderate to intense staining for BMP-2, -4, and -6 and BMPR-IA and BMPR-II, whereas splenic MKs showed no BMP immunostaining. Presence of BMP protein in the bone marrow of GATA-1low mice was more than that seen in controls, owing to an increased number of MKs and osteoblasts. The osteosclerosis seen in GATA-1low mice appeared not to be due to a reduced number of functional osteoclasts because the number of tartrate-resistant acid phosphatase-positive osteoclasts was greater in GATA-1low mice than in controls. Our findings demonstrate the presence of significant amounts of BMP-2, -4, and-6 along with their receptors in bone marrow MKs of WT and GATA-1low mice. The increased levels of BMPs appear to be a result of increased numbers of MKs in GATA-1low mice and may, in part, account for the stimulation of osteoblastic activity and resulting osteosclerosis.

Original languageEnglish (US)
Pages (from-to)745-752
Number of pages8
JournalJournal of Histochemistry and Cytochemistry
Volume55
Issue number7
DOIs
StatePublished - Jul 2007
Externally publishedYes

Fingerprint

Bone Morphogenetic Protein Receptors
Osteosclerosis
Megakaryocytes
Bone Marrow
Bone Morphogenetic Proteins
Primary Myelofibrosis
Bone Morphogenetic Protein 4
Bone Morphogenetic Protein 2
Osteoclasts
Myeloproliferative Disorders
Osteoblasts
Bone Marrow Cells
Real-Time Polymerase Chain Reaction
Intercellular Signaling Peptides and Proteins
Transcription Factors
Immunohistochemistry
Staining and Labeling

Keywords

  • Bone morphogenetic proteins
  • GATA-1
  • Megakaryocytes
  • Myelofibrosis
  • Osteoblasts
  • Osteosclerosis

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Expression of bone morphogenetic proteins and their receptors in the bone marrow megakaryocytes of GATA-1low mice : A possible role in osteosclerosis. / Garimella, Rama; Kacena, Melissa; Tague, Sarah E.; Wang, Jinxi; Horowitz, Mark C.; Anderson, H. Clarke.

In: Journal of Histochemistry and Cytochemistry, Vol. 55, No. 7, 07.2007, p. 745-752.

Research output: Contribution to journalArticle

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abstract = "The mechanism of osteosclerosis associated with myelofibrosis in megakaryocyte (MK)-related myeloproliferative disorders is largely unknown. However, growth factors released from the bone marrow cells, including from MKs, have been implicated in myelofibrosis, osteosclerosis, and angiogenesis. GATA-1 is a transcription factor required for normal MK development. GATA-1 deficiency in mice (GATA-1low) leads to increased megakaryocytic proliferation, followed by osteosclerosis and myelofibrosis. In this study we investigated the expression of bone morphogenetic proteins (BMPs) and BMP receptors and their possible role in the development of osteosclerosis in the MKs of 12-month-old GATA-1low mice by immunohistochemistry, cytomorphometry, and quantitative real-time PCR. Marrow MKs from both wild-type and GATA-1 low mice showed moderate to intense staining for BMP-2, -4, and -6 and BMPR-IA and BMPR-II, whereas splenic MKs showed no BMP immunostaining. Presence of BMP protein in the bone marrow of GATA-1low mice was more than that seen in controls, owing to an increased number of MKs and osteoblasts. The osteosclerosis seen in GATA-1low mice appeared not to be due to a reduced number of functional osteoclasts because the number of tartrate-resistant acid phosphatase-positive osteoclasts was greater in GATA-1low mice than in controls. Our findings demonstrate the presence of significant amounts of BMP-2, -4, and-6 along with their receptors in bone marrow MKs of WT and GATA-1low mice. The increased levels of BMPs appear to be a result of increased numbers of MKs in GATA-1low mice and may, in part, account for the stimulation of osteoblastic activity and resulting osteosclerosis.",
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AU - Horowitz, Mark C.

AU - Anderson, H. Clarke

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AB - The mechanism of osteosclerosis associated with myelofibrosis in megakaryocyte (MK)-related myeloproliferative disorders is largely unknown. However, growth factors released from the bone marrow cells, including from MKs, have been implicated in myelofibrosis, osteosclerosis, and angiogenesis. GATA-1 is a transcription factor required for normal MK development. GATA-1 deficiency in mice (GATA-1low) leads to increased megakaryocytic proliferation, followed by osteosclerosis and myelofibrosis. In this study we investigated the expression of bone morphogenetic proteins (BMPs) and BMP receptors and their possible role in the development of osteosclerosis in the MKs of 12-month-old GATA-1low mice by immunohistochemistry, cytomorphometry, and quantitative real-time PCR. Marrow MKs from both wild-type and GATA-1 low mice showed moderate to intense staining for BMP-2, -4, and -6 and BMPR-IA and BMPR-II, whereas splenic MKs showed no BMP immunostaining. Presence of BMP protein in the bone marrow of GATA-1low mice was more than that seen in controls, owing to an increased number of MKs and osteoblasts. The osteosclerosis seen in GATA-1low mice appeared not to be due to a reduced number of functional osteoclasts because the number of tartrate-resistant acid phosphatase-positive osteoclasts was greater in GATA-1low mice than in controls. Our findings demonstrate the presence of significant amounts of BMP-2, -4, and-6 along with their receptors in bone marrow MKs of WT and GATA-1low mice. The increased levels of BMPs appear to be a result of increased numbers of MKs in GATA-1low mice and may, in part, account for the stimulation of osteoblastic activity and resulting osteosclerosis.

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