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The Bone Matrix01:18

The Bone Matrix

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Bone contains a relatively small number of cells entrenched in a matrix of collagen fibers that provide an adherent surface for inorganic salt crystals. Both components of the matrix, organic and inorganic, contribute to the unusual properties of bone. Without collagen, bones would be brittle and shatter easily. Without mineral crystals, bones would flex and provide little support. This can be observed by an experiment: when the minerals of a bone are dissolved by soaking the bone in...
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In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
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A decreased body temperature can occur in patients with hypothermia and frostbite. Heat loss with extended cold exposure overpowers the body's ability to create heat, resulting in hypothermia. Core temperature readings help classify hypothermia. Mild hypothermia is temperatures between 32 °C (89.6 °F) and 35°C (95 °F) and is caused by impaired thermoregulation. Moderate hypothermia is temperatures between 28 C (82.4 °F) and 32 °C (89.6 °F) caused by...
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Bradycardia is a medical condition in which the heart rate is slower than normal. It occurs when the heart's natural pacemaker, the sinus node, generates slower electrical impulses than the standard rhythm. In adults, bradycardia is diagnosed when the pulse rate falls below 60 beats per minute, indicating a deviation from the normal heart rate range.
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Synthesis and decomposition are two types of redox reactions. Synthesis means to make something, whereas decomposition means to break something. The reactions are accompanied by chemical and energy changes. 
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Erratum: [Corrigendum] Imatinib mesylate and nilotinib decrease synthesis of bone matrix <i>in vitro</i>.

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Imatinib mesylate and nilotinib decrease synthesis of bone matrix in vitro.

Lysann Michaela Kroschwald1,2, Josephine Tabea Tauer3, Sonja Ingrid Kroschwald4,5

  • 1Department of Dermatology, Medical Faculty, Technical University Dresden, D-01307 Dresden, Germany.

Oncology Letters
|August 20, 2019
PubMed
Summary
This summary is machine-generated.

Tyrosine kinase inhibitors (TKIs) like imatinib and nilotinib used for chronic myeloid leukemia (CML) treatment directly harm bone cells. These TKIs inhibit osteoblast function and promote bone breakdown, suggesting a need for bone health monitoring in CML patients.

Keywords:
bonechronic myeloid leukemiaimatinibnilotinibosteoblastogenesisreceptor activator of nuclear factor κB ligand

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Area of Science:

  • Biochemistry
  • Oncology
  • Cell Biology

Background:

  • Tyrosine kinase inhibitors (TKIs), including imatinib (IMA) and nilotinib (NIL), are vital for treating chronic myeloid leukemia (CML) by inhibiting the BCR-ABL1 fusion protein.
  • Pediatric patients on long-term IMA treatment often experience skeletal side effects, and in vitro studies indicate TKIs disrupt vitamin D metabolism, potentially worsening bone health.

Purpose of the Study:

  • To investigate the direct impact of TKIs (IMA and NIL) on the function of human osteoblastic cells.
  • To assess the effects of TKIs on osteoblast mineralization and the expression of key genes regulating bone metabolism and osteoclastogenesis.

Main Methods:

  • Human osteoblastic SaOS-2 cells were treated with imatinib (IMA) or nilotinib (NIL).
  • Assessed effects on mineralization capacity.
  • Measured mRNA expression of osteoblast markers, Wnt signaling pathway genes, receptor activator of nuclear factor κB ligand (RANKL), and osteoprotegerin (OPG).

Main Results:

  • Both IMA and NIL significantly inhibited SaOS-2 cell mineralization.
  • TKIs downregulated osteoblast differentiation markers (alkaline phosphatase, osteocalcin, osterix) and Wnt signaling pathway genes.
  • Nilotinib (NIL) demonstrated greater potency than imatinib (IMA).
  • Both TKIs increased the RANKL/OPG ratio, favoring osteoclastogenesis.

Conclusions:

  • TKIs IMA and NIL directly inhibit osteoblast differentiation and function.
  • TKIs promote a pro-osteoclastogenic environment via the RANKL-OPG axis.
  • Routine monitoring of bone health in CML patients undergoing TKI therapy is warranted.