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Mice with Targeted Knockout of Tetraspanin 3 Exhibit Reduced Trabecular Bone Mass Caused by Decreased Osteoblast Functions

Tetraspanin3 (TSPAN3) was identified as a binding partner of claudin11 (CLDN11) in osteoblasts and other cell types. Mice with targeted disruption of Cldn11 exhibited trabecular bone mass deficit caused by reduced bone formation and osteoblast function. To determine if the disruption of CLDN11 inter...

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Autores principales: Xing, Weirong, Pourteymoor, Sheila, Kesavan, Chandrasekhar, Gomez, Gustavo A., Mohan, Subburaman
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946581/
https://www.ncbi.nlm.nih.gov/pubmed/35326428
http://dx.doi.org/10.3390/cells11060977
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author Xing, Weirong
Pourteymoor, Sheila
Kesavan, Chandrasekhar
Gomez, Gustavo A.
Mohan, Subburaman
author_facet Xing, Weirong
Pourteymoor, Sheila
Kesavan, Chandrasekhar
Gomez, Gustavo A.
Mohan, Subburaman
author_sort Xing, Weirong
collection PubMed
description Tetraspanin3 (TSPAN3) was identified as a binding partner of claudin11 (CLDN11) in osteoblasts and other cell types. Mice with targeted disruption of Cldn11 exhibited trabecular bone mass deficit caused by reduced bone formation and osteoblast function. To determine if the disruption of CLDN11 interacting protein gene Tspan3 results in a similar skeletal phenotype as that of Cldn11 knockout (KO) mice, we generated homozygous Tspan3 KO and heterozygous control mice and characterized their skeletal phenotypes at 13 weeks of age. Micro-CT measurements of the secondary spongiosa of the distal femur revealed 17% and 29% reduction in trabecular bone volume adjusted for tissue volume (BV/TV) in the male and female mice, respectively. Similarly, trabecular BV/TV of the proximal tibia was reduced by 19% and 20% in the male and female mice, respectively. The reduced trabecular bone mass was caused primarily by reduced trabecular thickness and number, and increased trabecular spacing. Consistent with the reduced bone formation as confirmed by histomorphometry analyses, serum alkaline phosphatase was reduced by 11% in the KO mice as compared with controls. Our findings indicate that TSPAN3 is an important positive regulator of osteoblast function and trabecular bone mass, and the interaction of TSPAN3 with CLDN11 could contribute in part to the bone forming effects of Cldn11 in mice.
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spelling pubmed-89465812022-03-25 Mice with Targeted Knockout of Tetraspanin 3 Exhibit Reduced Trabecular Bone Mass Caused by Decreased Osteoblast Functions Xing, Weirong Pourteymoor, Sheila Kesavan, Chandrasekhar Gomez, Gustavo A. Mohan, Subburaman Cells Communication Tetraspanin3 (TSPAN3) was identified as a binding partner of claudin11 (CLDN11) in osteoblasts and other cell types. Mice with targeted disruption of Cldn11 exhibited trabecular bone mass deficit caused by reduced bone formation and osteoblast function. To determine if the disruption of CLDN11 interacting protein gene Tspan3 results in a similar skeletal phenotype as that of Cldn11 knockout (KO) mice, we generated homozygous Tspan3 KO and heterozygous control mice and characterized their skeletal phenotypes at 13 weeks of age. Micro-CT measurements of the secondary spongiosa of the distal femur revealed 17% and 29% reduction in trabecular bone volume adjusted for tissue volume (BV/TV) in the male and female mice, respectively. Similarly, trabecular BV/TV of the proximal tibia was reduced by 19% and 20% in the male and female mice, respectively. The reduced trabecular bone mass was caused primarily by reduced trabecular thickness and number, and increased trabecular spacing. Consistent with the reduced bone formation as confirmed by histomorphometry analyses, serum alkaline phosphatase was reduced by 11% in the KO mice as compared with controls. Our findings indicate that TSPAN3 is an important positive regulator of osteoblast function and trabecular bone mass, and the interaction of TSPAN3 with CLDN11 could contribute in part to the bone forming effects of Cldn11 in mice. MDPI 2022-03-12 /pmc/articles/PMC8946581/ /pubmed/35326428 http://dx.doi.org/10.3390/cells11060977 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Xing, Weirong
Pourteymoor, Sheila
Kesavan, Chandrasekhar
Gomez, Gustavo A.
Mohan, Subburaman
Mice with Targeted Knockout of Tetraspanin 3 Exhibit Reduced Trabecular Bone Mass Caused by Decreased Osteoblast Functions
title Mice with Targeted Knockout of Tetraspanin 3 Exhibit Reduced Trabecular Bone Mass Caused by Decreased Osteoblast Functions
title_full Mice with Targeted Knockout of Tetraspanin 3 Exhibit Reduced Trabecular Bone Mass Caused by Decreased Osteoblast Functions
title_fullStr Mice with Targeted Knockout of Tetraspanin 3 Exhibit Reduced Trabecular Bone Mass Caused by Decreased Osteoblast Functions
title_full_unstemmed Mice with Targeted Knockout of Tetraspanin 3 Exhibit Reduced Trabecular Bone Mass Caused by Decreased Osteoblast Functions
title_short Mice with Targeted Knockout of Tetraspanin 3 Exhibit Reduced Trabecular Bone Mass Caused by Decreased Osteoblast Functions
title_sort mice with targeted knockout of tetraspanin 3 exhibit reduced trabecular bone mass caused by decreased osteoblast functions
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946581/
https://www.ncbi.nlm.nih.gov/pubmed/35326428
http://dx.doi.org/10.3390/cells11060977
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