Steroids and Malignancy Increase Local Heparanase and Decrease Markers of Osteoblast Activity in Bone Tissue Microcirculation
Bone metastasis and steroids are known to activate the coagulation system and induce osteoporosis, pathological bone fractures, and bone pain. Heparanase is a protein known to enhance the hemostatic system and to promote angiogenesis, metastasis, and inflammation. The objective of the present study...
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2024-11-01
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| author | Keren Asayag Eli Peled Mai Assalia Yonatan Crispel Chen Yanovich Haim Cohen Anat Keren-Politansky Yona Nadir |
| author_facet | Keren Asayag Eli Peled Mai Assalia Yonatan Crispel Chen Yanovich Haim Cohen Anat Keren-Politansky Yona Nadir |
| author_sort | Keren Asayag |
| collection | DOAJ |
| description | Bone metastasis and steroids are known to activate the coagulation system and induce osteoporosis, pathological bone fractures, and bone pain. Heparanase is a protein known to enhance the hemostatic system and to promote angiogenesis, metastasis, and inflammation. The objective of the present study was to evaluate the effects of steroids and malignancy on the coagulation factors and osteoblast activity in the bone tissue. The effects of dexacort and malignant medium were evaluated in osteoblasts derived from human bone marrow mesenchymal stem cells and human umbilical vein endothelial cells (HUVECs). The bones of mice treated with dexacort for 1 month were studied. Bone biopsies of ten patients with bone metastasis, ten with steroid-induced avascular necrosis (AVN), and ten with osteoarthritis were compared to ten controls. We found that dexacort and malignant medium significantly increased the heparanase levels in osteoblasts and HUVECs and decreased the levels of alkaline phosphatase (ALKP). Peptide 16AC, derived from heparanase, which interacts with tissue factor (TF), further increased the effect, while peptide 6, which inhibits interactions between heparanase and TF, reversed the effect in these cells. The bone microcirculation of mice treated with dexacort exhibited significantly higher levels of heparanase, TF, TF pathway inhibitor (TFPI), TFPI-2, thrombin, and syndecan-1, but reduced levels of osteocalcin and ALKP. The pathological human bone biopsies’ microcirculation exhibited significantly dilated blood vessels and higher levels of heparanase, TF, TFPI, TFPI-2, and fibrin. In summary, steroids and malignancy increased the activation of the coagulation system in the bone microcirculation and reduced the osteoblast activity. Heparanase inhibitors should be further investigated to attenuate bone fractures and pain. |
| format | Article |
| id | doaj-art-db18c7a7d0e64a31b5fdb38980f3d71b |
| institution | OA Journals |
| issn | 2218-273X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
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| series | Biomolecules |
| spelling | doaj-art-db18c7a7d0e64a31b5fdb38980f3d71b2025-08-20T02:00:56ZengMDPI AGBiomolecules2218-273X2024-11-011412150610.3390/biom14121506Steroids and Malignancy Increase Local Heparanase and Decrease Markers of Osteoblast Activity in Bone Tissue MicrocirculationKeren Asayag0Eli Peled1Mai Assalia2Yonatan Crispel3Chen Yanovich4Haim Cohen5Anat Keren-Politansky6Yona Nadir7Thrombosis and Hemostasis Unit, Rambam Health Care Campus, Haifa 3109601, IsraelThe Ruth and Bruce Rappaport Faculty of Medicine, Israel Institute of Technology—Technion, Haifa 3109601, IsraelThrombosis and Hemostasis Unit, Rambam Health Care Campus, Haifa 3109601, IsraelThrombosis and Hemostasis Unit, Rambam Health Care Campus, Haifa 3109601, IsraelThrombosis and Hemostasis Unit, Rambam Health Care Campus, Haifa 3109601, IsraelThrombosis and Hemostasis Unit, Rambam Health Care Campus, Haifa 3109601, IsraelThrombosis and Hemostasis Unit, Rambam Health Care Campus, Haifa 3109601, IsraelThrombosis and Hemostasis Unit, Rambam Health Care Campus, Haifa 3109601, IsraelBone metastasis and steroids are known to activate the coagulation system and induce osteoporosis, pathological bone fractures, and bone pain. Heparanase is a protein known to enhance the hemostatic system and to promote angiogenesis, metastasis, and inflammation. The objective of the present study was to evaluate the effects of steroids and malignancy on the coagulation factors and osteoblast activity in the bone tissue. The effects of dexacort and malignant medium were evaluated in osteoblasts derived from human bone marrow mesenchymal stem cells and human umbilical vein endothelial cells (HUVECs). The bones of mice treated with dexacort for 1 month were studied. Bone biopsies of ten patients with bone metastasis, ten with steroid-induced avascular necrosis (AVN), and ten with osteoarthritis were compared to ten controls. We found that dexacort and malignant medium significantly increased the heparanase levels in osteoblasts and HUVECs and decreased the levels of alkaline phosphatase (ALKP). Peptide 16AC, derived from heparanase, which interacts with tissue factor (TF), further increased the effect, while peptide 6, which inhibits interactions between heparanase and TF, reversed the effect in these cells. The bone microcirculation of mice treated with dexacort exhibited significantly higher levels of heparanase, TF, TF pathway inhibitor (TFPI), TFPI-2, thrombin, and syndecan-1, but reduced levels of osteocalcin and ALKP. The pathological human bone biopsies’ microcirculation exhibited significantly dilated blood vessels and higher levels of heparanase, TF, TFPI, TFPI-2, and fibrin. In summary, steroids and malignancy increased the activation of the coagulation system in the bone microcirculation and reduced the osteoblast activity. Heparanase inhibitors should be further investigated to attenuate bone fractures and pain.https://www.mdpi.com/2218-273X/14/12/1506bonemicrocirculationthrombosisheparanasesteroidsmalignancy |
| spellingShingle | Keren Asayag Eli Peled Mai Assalia Yonatan Crispel Chen Yanovich Haim Cohen Anat Keren-Politansky Yona Nadir Steroids and Malignancy Increase Local Heparanase and Decrease Markers of Osteoblast Activity in Bone Tissue Microcirculation Biomolecules bone microcirculation thrombosis heparanase steroids malignancy |
| title | Steroids and Malignancy Increase Local Heparanase and Decrease Markers of Osteoblast Activity in Bone Tissue Microcirculation |
| title_full | Steroids and Malignancy Increase Local Heparanase and Decrease Markers of Osteoblast Activity in Bone Tissue Microcirculation |
| title_fullStr | Steroids and Malignancy Increase Local Heparanase and Decrease Markers of Osteoblast Activity in Bone Tissue Microcirculation |
| title_full_unstemmed | Steroids and Malignancy Increase Local Heparanase and Decrease Markers of Osteoblast Activity in Bone Tissue Microcirculation |
| title_short | Steroids and Malignancy Increase Local Heparanase and Decrease Markers of Osteoblast Activity in Bone Tissue Microcirculation |
| title_sort | steroids and malignancy increase local heparanase and decrease markers of osteoblast activity in bone tissue microcirculation |
| topic | bone microcirculation thrombosis heparanase steroids malignancy |
| url | https://www.mdpi.com/2218-273X/14/12/1506 |
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