Cargando…

The Osteocyte as the New Discovery of Therapeutic Options in Rare Bone Diseases

Osteocytes are the most abundant (~95%) cells in bone with the longest half-life (~25 years) in humans. In the past osteocytes have been regarded as vestigial cells in bone, since they are buried inside the tough bone matrix. However, during the last 30 years it has become clear that osteocytes are...

Descripción completa

Detalles Bibliográficos
Autores principales: Pathak, Janak L., Bravenboer, Nathalie, Klein-Nulend, Jenneke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360678/
https://www.ncbi.nlm.nih.gov/pubmed/32733380
http://dx.doi.org/10.3389/fendo.2020.00405
_version_ 1783559259912404992
author Pathak, Janak L.
Bravenboer, Nathalie
Klein-Nulend, Jenneke
author_facet Pathak, Janak L.
Bravenboer, Nathalie
Klein-Nulend, Jenneke
author_sort Pathak, Janak L.
collection PubMed
description Osteocytes are the most abundant (~95%) cells in bone with the longest half-life (~25 years) in humans. In the past osteocytes have been regarded as vestigial cells in bone, since they are buried inside the tough bone matrix. However, during the last 30 years it has become clear that osteocytes are as important as bone forming osteoblasts and bone resorbing osteoclasts in maintaining bone homeostasis. The osteocyte cell body and dendritic processes reside in bone in a complex lacuno-canalicular system, which allows the direct networking of osteocytes to their neighboring osteocytes, osteoblasts, osteoclasts, bone marrow, blood vessels, and nerves. Mechanosensing of osteocytes translates the applied mechanical force on bone to cellular signaling and regulation of bone adaptation. The osteocyte lacuno-canalicular system is highly efficient in transferring external mechanical force on bone to the osteocyte cell body and dendritic processes via displacement of fluid in the lacuno-canalicular space. Osteocyte mechanotransduction regulates the formation and function of the osteoblasts and osteoclasts to maintain bone homeostasis. Osteocytes produce a variety of proteins and signaling molecules such as sclerostin, cathepsin K, Wnts, DKK1, DMP1, IGF1, and RANKL/OPG to regulate osteoblast and osteoclast activity. Various genetic abnormality-associated rare bone diseases are related to disrupted osteocyte functions, including sclerosteosis, van Buchem disease, hypophosphatemic rickets, and WNT1 and plastin3 mutation-related disorders. Meticulous studies during the last 15 years on disrupted osteocyte function in rare bone diseases guided for the development of various novel therapeutic agents to treat bone diseases. Studies on genetic, molecular, and cellular mechanisms of sclerosteosis and van Buchem disease revealed a role for sclerostin in bone homeostasis, which led to the development of the sclerostin antibody to treat osteoporosis and other bone degenerative diseases. The mechanism of many other rare bone diseases and the role of the osteocyte in the development of such conditions still needs to be investigated. In this review, we mainly discuss the knowledge obtained during the last 30 years on the role of the osteocyte in rare bone diseases. We speculate about future research directions to develop novel therapeutic drugs targeting osteocyte functions to treat both common and rare bone diseases.
format Online
Article
Text
id pubmed-7360678
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-73606782020-07-29 The Osteocyte as the New Discovery of Therapeutic Options in Rare Bone Diseases Pathak, Janak L. Bravenboer, Nathalie Klein-Nulend, Jenneke Front Endocrinol (Lausanne) Endocrinology Osteocytes are the most abundant (~95%) cells in bone with the longest half-life (~25 years) in humans. In the past osteocytes have been regarded as vestigial cells in bone, since they are buried inside the tough bone matrix. However, during the last 30 years it has become clear that osteocytes are as important as bone forming osteoblasts and bone resorbing osteoclasts in maintaining bone homeostasis. The osteocyte cell body and dendritic processes reside in bone in a complex lacuno-canalicular system, which allows the direct networking of osteocytes to their neighboring osteocytes, osteoblasts, osteoclasts, bone marrow, blood vessels, and nerves. Mechanosensing of osteocytes translates the applied mechanical force on bone to cellular signaling and regulation of bone adaptation. The osteocyte lacuno-canalicular system is highly efficient in transferring external mechanical force on bone to the osteocyte cell body and dendritic processes via displacement of fluid in the lacuno-canalicular space. Osteocyte mechanotransduction regulates the formation and function of the osteoblasts and osteoclasts to maintain bone homeostasis. Osteocytes produce a variety of proteins and signaling molecules such as sclerostin, cathepsin K, Wnts, DKK1, DMP1, IGF1, and RANKL/OPG to regulate osteoblast and osteoclast activity. Various genetic abnormality-associated rare bone diseases are related to disrupted osteocyte functions, including sclerosteosis, van Buchem disease, hypophosphatemic rickets, and WNT1 and plastin3 mutation-related disorders. Meticulous studies during the last 15 years on disrupted osteocyte function in rare bone diseases guided for the development of various novel therapeutic agents to treat bone diseases. Studies on genetic, molecular, and cellular mechanisms of sclerosteosis and van Buchem disease revealed a role for sclerostin in bone homeostasis, which led to the development of the sclerostin antibody to treat osteoporosis and other bone degenerative diseases. The mechanism of many other rare bone diseases and the role of the osteocyte in the development of such conditions still needs to be investigated. In this review, we mainly discuss the knowledge obtained during the last 30 years on the role of the osteocyte in rare bone diseases. We speculate about future research directions to develop novel therapeutic drugs targeting osteocyte functions to treat both common and rare bone diseases. Frontiers Media S.A. 2020-07-08 /pmc/articles/PMC7360678/ /pubmed/32733380 http://dx.doi.org/10.3389/fendo.2020.00405 Text en Copyright © 2020 Pathak, Bravenboer and Klein-Nulend. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Pathak, Janak L.
Bravenboer, Nathalie
Klein-Nulend, Jenneke
The Osteocyte as the New Discovery of Therapeutic Options in Rare Bone Diseases
title The Osteocyte as the New Discovery of Therapeutic Options in Rare Bone Diseases
title_full The Osteocyte as the New Discovery of Therapeutic Options in Rare Bone Diseases
title_fullStr The Osteocyte as the New Discovery of Therapeutic Options in Rare Bone Diseases
title_full_unstemmed The Osteocyte as the New Discovery of Therapeutic Options in Rare Bone Diseases
title_short The Osteocyte as the New Discovery of Therapeutic Options in Rare Bone Diseases
title_sort osteocyte as the new discovery of therapeutic options in rare bone diseases
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360678/
https://www.ncbi.nlm.nih.gov/pubmed/32733380
http://dx.doi.org/10.3389/fendo.2020.00405
work_keys_str_mv AT pathakjanakl theosteocyteasthenewdiscoveryoftherapeuticoptionsinrarebonediseases
AT bravenboernathalie theosteocyteasthenewdiscoveryoftherapeuticoptionsinrarebonediseases
AT kleinnulendjenneke theosteocyteasthenewdiscoveryoftherapeuticoptionsinrarebonediseases
AT pathakjanakl osteocyteasthenewdiscoveryoftherapeuticoptionsinrarebonediseases
AT bravenboernathalie osteocyteasthenewdiscoveryoftherapeuticoptionsinrarebonediseases
AT kleinnulendjenneke osteocyteasthenewdiscoveryoftherapeuticoptionsinrarebonediseases