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Steroids and Malignancy Increase Local Heparanase and Decrease Markers of Osteoblast Activity in Bone Tissue

Keren Asayag1,2, Eli Peled2,3, Mai Assalia1,2

  • 1Thrombosis and Hemostasis Unit, Rambam Health Care Campus, Haifa 3109601, Israel.

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Summary
This summary is machine-generated.

Steroids and malignancy activate blood clotting in bone, reducing bone-building activity and increasing fracture risk. Heparanase inhibitors may help prevent bone pain and fractures.

Keywords:
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Area of Science:

  • Biochemistry
  • Oncology
  • Orthopedics

Background:

  • Steroids and malignancy activate coagulation and induce bone loss, fractures, and pain.
  • Heparanase enhances hemostasis, angiogenesis, metastasis, and inflammation.

Purpose of the Study:

  • To evaluate steroid and malignancy effects on coagulation factors and osteoblast activity in bone tissue.
  • To investigate the role of heparanase in these processes.

Main Methods:

  • In vitro studies using osteoblasts and HUVECs exposed to dexacort and malignant medium.
  • In vivo studies in mice treated with dexacort.
  • Analysis of bone biopsies from patients with bone metastasis, AVN, osteoarthritis, and controls.

Main Results:

  • Dexacort and malignant medium increased heparanase levels and decreased alkaline phosphatase (ALKP) in cells.
  • Heparanase-derived peptides modulated these effects.
  • Mice and human bone biopsies showed increased heparanase, coagulation factors (TF, TFPI, TFPI-2, thrombin, fibrin), and dilated blood vessels, with reduced osteoblast markers (osteocalcin, ALKP).

Conclusions:

  • Steroids and malignancy activate bone microcirculation coagulation and impair osteoblast activity.
  • Heparanase plays a key role in these pathological changes.
  • Heparanase inhibitors warrant further investigation for managing bone fractures and pain.