Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2020 Sep 19;2(11):668–679. doi: 10.1096/fba.2020-00058

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

©2020 The Authors. FASEB BioAdvances published by The Federation of American Societies for Experimental Biology

This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

PMC Copyright notice

The regulation of bone homeostasis by cellular signalling molecules. Osteoblasts and chondrocytes originate from common MSC lineage precursors. Runx2, Osx, ATF4 are considered master genes for osteoblast differentiation. Ihh and Wnt/β‐catenin are also supporting signalling molecules in osteoblastogenesis. In response to various stressors such as oxidative stress, genomic instability and telomere shortening, osteocytes can be converted into osteocyte senescent cells which have SASP factor. The SASP upregulates NF‐κB and increases pro‐inflammatory factors such as IL‐1α. As a result, senescent cells and the SASP contribute to age‐related frailty and a number of age‐associated chronic diseases including osteoporosis. During osteoclast differentiation, osteoclasts derive from by the fusion of mononuclear progenitors of the monocyte/macrophage family, and osteocytes are non‐proliferative differentiated cells of the osteoblast lineage. M‐CSF and RANKL are essential external stimuli for osteoclastogenesis. PU.1, MITF, NF‐κB, AP‐1 and NFATc1 are essential for differentiation of functional osteoclasts. CT negatively regulates the osteoclast expression of spinster 2 (Spns2), which encodes a transporter for the signalling lipid sphingosine 1‐phosphate (S1P). CT suppresses Spns2 expression and reduces S1P release from osteoclasts. Sphingosine, derived from the membrane lipid sphingomyelin through intermediate ceramide, is phosphorylated to S1P by sphingosine kinases (Sphk1 and 2). S1P is either degraded by sphingosine lyase or secreted through obligatory interaction with Spns2 which is reduced by calcitonin. S1P acts through receptor S1PR3 in the osteoblast to increase osteoblast differentiation and bone formation. The osteocyte (stellate shaped blue cells on the right) expresses several membrane receptors including receptors including PTH and others and controls both osteoblast and osteoclast functions though sclerostin and RANKL. Osteocytes also secrete factors involved in phosphate homeostasis. indicates upregulation and indicates down‐regulation.

Inline graphic — The regulation of bone homeostasis by cellular signalling molecules. Osteoblasts and chondrocytes originate from common MSC lineage precursors. Runx2, Osx, ATF4 are considered master genes for osteoblast differentiation. Ihh and Wnt/β‐catenin are also supporting signalling molecules in osteoblastogenesis. In response to various stressors such as oxidative stress, genomic instability and telomere shortening, osteocytes can be converted into osteocyte senescent cells which have SASP factor. The SASP upregulates NF‐κB and increases pro‐inflammatory factors such as IL‐1α. As a result, senescent cells and the SASP contribute to age‐related frailty and a number of age‐associated chronic diseases including osteoporosis. During osteoclast differentiation, osteoclasts derive from by the fusion of mononuclear progenitors of the monocyte/macrophage family, and osteocytes are non‐proliferative differentiated cells of the osteoblast lineage. M‐CSF and RANKL are essential external stimuli for osteoclastogenesis. PU.1, MITF, NF‐κB, AP‐1 and NFATc1 are essential for differentiation of functional osteoclasts. CT negatively regulates the osteoclast expression of spinster 2 (Spns2), which encodes a transporter for the signalling lipid sphingosine 1‐phosphate (S1P). CT suppresses Spns2 expression and reduces S1P release from osteoclasts. Sphingosine, derived from the membrane lipid sphingomyelin through intermediate ceramide, is phosphorylated to S1P by sphingosine kinases (Sphk1 and 2). S1P is either degraded by sphingosine lyase or secreted through obligatory interaction with Spns2 which is reduced by calcitonin. S1P acts through receptor S1PR3 in the osteoblast to increase osteoblast differentiation and bone formation. The osteocyte (stellate shaped blue cells on the right) expresses several membrane receptors including receptors including PTH and others and controls both osteoblast and osteoclast functions though sclerostin and RANKL. Osteocytes also secrete factors involved in phosphate homeostasis. indicates upregulation and indicates down‐regulation.