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From Osteoclast Differentiation to Osteonecrosis of the Jaw: Molecular and Clinical Insights
Bone physiology relies on the delicate balance between resorption and formation of its tissue. Bone resorption depends on a process called osteoclastogenesis in which bone-resorbing cells, i.e., osteoclasts, are produced by the differentiation of more undifferentiated progenitors and precursors. Thi...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801843/ https://www.ncbi.nlm.nih.gov/pubmed/31590328 http://dx.doi.org/10.3390/ijms20194925 |
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author | Anesi, Alexandre Generali, Luigi Sandoni, Laura Pozzi, Samantha Grande, Alexis |
author_facet | Anesi, Alexandre Generali, Luigi Sandoni, Laura Pozzi, Samantha Grande, Alexis |
author_sort | Anesi, Alexandre |
collection | PubMed |
description | Bone physiology relies on the delicate balance between resorption and formation of its tissue. Bone resorption depends on a process called osteoclastogenesis in which bone-resorbing cells, i.e., osteoclasts, are produced by the differentiation of more undifferentiated progenitors and precursors. This process is governed by two main factors, monocyte-colony stimulating factor (M-CSF) and receptor activator of NFκB ligand (RANKL). While the former exerts a proliferating effect on progenitors/precursors, the latter triggers a differentiation effect on more mature cells of the same lineage. Bone homeostasis requires a perfect space–time coordination of the involved signals. When osteoclastogenesis is poorly balanced with the differentiation of the bone forming counterparts, i.e., osteoblasts, physiological bone remodelling can turn into a pathological state, causing the systematic disruption of bone tissue which results in osteopenia or osteolysis. Examples of these conditions are represented by osteoporosis, Paget’s disease, bone metastasis, and multiple myeloma. Therefore, drugs targeting osteoclastogenesis, such as bisphosphonates and an anti-RANKL monoclonal antibody, have been developed and are currently used in the treatment of such diseases. Despite their demonstrated therapeutic efficacy, these agents are unfortunately not devoid of side effects. In this regard, a condition called osteonecrosis of the jaw (ONJ) has been recently correlated with anti-resorptive therapy. In this review we will address the involvement of osteoclasts and osteoclast-related factors in the pathogenesis of ONJ. It is to be hoped that a better understanding of the biological mechanisms underlying bone remodelling will help in the design a medical therapeutic approach for ONJ as an alternative to surgical procedures. |
format | Online Article Text |
id | pubmed-6801843 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68018432019-10-31 From Osteoclast Differentiation to Osteonecrosis of the Jaw: Molecular and Clinical Insights Anesi, Alexandre Generali, Luigi Sandoni, Laura Pozzi, Samantha Grande, Alexis Int J Mol Sci Review Bone physiology relies on the delicate balance between resorption and formation of its tissue. Bone resorption depends on a process called osteoclastogenesis in which bone-resorbing cells, i.e., osteoclasts, are produced by the differentiation of more undifferentiated progenitors and precursors. This process is governed by two main factors, monocyte-colony stimulating factor (M-CSF) and receptor activator of NFκB ligand (RANKL). While the former exerts a proliferating effect on progenitors/precursors, the latter triggers a differentiation effect on more mature cells of the same lineage. Bone homeostasis requires a perfect space–time coordination of the involved signals. When osteoclastogenesis is poorly balanced with the differentiation of the bone forming counterparts, i.e., osteoblasts, physiological bone remodelling can turn into a pathological state, causing the systematic disruption of bone tissue which results in osteopenia or osteolysis. Examples of these conditions are represented by osteoporosis, Paget’s disease, bone metastasis, and multiple myeloma. Therefore, drugs targeting osteoclastogenesis, such as bisphosphonates and an anti-RANKL monoclonal antibody, have been developed and are currently used in the treatment of such diseases. Despite their demonstrated therapeutic efficacy, these agents are unfortunately not devoid of side effects. In this regard, a condition called osteonecrosis of the jaw (ONJ) has been recently correlated with anti-resorptive therapy. In this review we will address the involvement of osteoclasts and osteoclast-related factors in the pathogenesis of ONJ. It is to be hoped that a better understanding of the biological mechanisms underlying bone remodelling will help in the design a medical therapeutic approach for ONJ as an alternative to surgical procedures. MDPI 2019-10-04 /pmc/articles/PMC6801843/ /pubmed/31590328 http://dx.doi.org/10.3390/ijms20194925 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Anesi, Alexandre Generali, Luigi Sandoni, Laura Pozzi, Samantha Grande, Alexis From Osteoclast Differentiation to Osteonecrosis of the Jaw: Molecular and Clinical Insights |
title | From Osteoclast Differentiation to Osteonecrosis of the Jaw: Molecular and Clinical Insights |
title_full | From Osteoclast Differentiation to Osteonecrosis of the Jaw: Molecular and Clinical Insights |
title_fullStr | From Osteoclast Differentiation to Osteonecrosis of the Jaw: Molecular and Clinical Insights |
title_full_unstemmed | From Osteoclast Differentiation to Osteonecrosis of the Jaw: Molecular and Clinical Insights |
title_short | From Osteoclast Differentiation to Osteonecrosis of the Jaw: Molecular and Clinical Insights |
title_sort | from osteoclast differentiation to osteonecrosis of the jaw: molecular and clinical insights |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801843/ https://www.ncbi.nlm.nih.gov/pubmed/31590328 http://dx.doi.org/10.3390/ijms20194925 |
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