Mutation of the galectin‐3 glycan‐binding domain (Lgals3‐R200S) enhances cortical bone expansion in male mice and trabecular bone mass in female mice
We previously observed that genomic loss of galectin‐3 (Gal‐3; encoded by Lgals3) in mice has a significant protective effect on age‐related bone loss. Gal‐3 has both intracellular and extracellular functionality, and we wanted to assess whether the affect we observed in the Lgals3 knockout (KO) mic...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-10-01
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| Series: | FEBS Open Bio |
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| Online Access: | https://doi.org/10.1002/2211-5463.13483 |
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| author | Kevin A. Maupin Cassandra R. Diegel Payton D. Stevens Daniel Dick VAI Vivarium and Transgenic Core Bart O. Williams |
| author_facet | Kevin A. Maupin Cassandra R. Diegel Payton D. Stevens Daniel Dick VAI Vivarium and Transgenic Core Bart O. Williams |
| author_sort | Kevin A. Maupin |
| collection | DOAJ |
| description | We previously observed that genomic loss of galectin‐3 (Gal‐3; encoded by Lgals3) in mice has a significant protective effect on age‐related bone loss. Gal‐3 has both intracellular and extracellular functionality, and we wanted to assess whether the affect we observed in the Lgals3 knockout (KO) mice could be attributed to the ability of Gal‐3 to bind glycoproteins. Mutation of a highly conserved arginine to a serine in human Gal‐3 (LGALS3‐R186S) blocks glycan binding and secretion. We generated mice with the equivalent mutation (Lgals3‐R200S) and observed a subsequent reduction in Gal‐3 secretion from mouse embryonic fibroblasts and in circulating blood. When examining bone structure in aged mice, we noticed some similarities to the Lgals3‐KO mice and some differences. First, we observed greater bone mass in Lgals3‐R200S mutant mice, as was previously observed in Lgals3‐KO mice. Like Lgals3‐KO mice, significantly increased trabecular bone mass was only observed in female Lgals3‐R200S mice. These results suggest that the greater bone mass observed is driven by the loss of extracellular Gal‐3 functionality. However, the results from our cortical bone expansion data showed a sex‐dependent difference, with only male Lgals3‐KO mice having an increased response, contrasting with our earlier study. These notable sex differences suggest a potential role for sex hormones, most likely androgen signaling, being involved. In summary, our results suggest that targeting extracellular Gal‐3 function may be a suitable treatment for age‐related loss of bone mass. |
| first_indexed | 2024-04-11T09:21:35Z |
| format | Article |
| id | doaj.art-874c659405224149baacd2786c3095d3 |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-04-11T09:21:35Z |
| publishDate | 2022-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-874c659405224149baacd2786c3095d32022-12-22T04:32:10ZengWileyFEBS Open Bio2211-54632022-10-0112101717172810.1002/2211-5463.13483Mutation of the galectin‐3 glycan‐binding domain (Lgals3‐R200S) enhances cortical bone expansion in male mice and trabecular bone mass in female miceKevin A. Maupin0Cassandra R. Diegel1Payton D. Stevens2Daniel Dick3VAI Vivarium and Transgenic Core4Bart O. Williams5Van Andel Institute Grand Rapids MI USAVan Andel Institute Grand Rapids MI USAVan Andel Institute Grand Rapids MI USAVan Andel Institute Grand Rapids MI USAVan Andel Institute Grand Rapids MI USAVan Andel Institute Grand Rapids MI USAWe previously observed that genomic loss of galectin‐3 (Gal‐3; encoded by Lgals3) in mice has a significant protective effect on age‐related bone loss. Gal‐3 has both intracellular and extracellular functionality, and we wanted to assess whether the affect we observed in the Lgals3 knockout (KO) mice could be attributed to the ability of Gal‐3 to bind glycoproteins. Mutation of a highly conserved arginine to a serine in human Gal‐3 (LGALS3‐R186S) blocks glycan binding and secretion. We generated mice with the equivalent mutation (Lgals3‐R200S) and observed a subsequent reduction in Gal‐3 secretion from mouse embryonic fibroblasts and in circulating blood. When examining bone structure in aged mice, we noticed some similarities to the Lgals3‐KO mice and some differences. First, we observed greater bone mass in Lgals3‐R200S mutant mice, as was previously observed in Lgals3‐KO mice. Like Lgals3‐KO mice, significantly increased trabecular bone mass was only observed in female Lgals3‐R200S mice. These results suggest that the greater bone mass observed is driven by the loss of extracellular Gal‐3 functionality. However, the results from our cortical bone expansion data showed a sex‐dependent difference, with only male Lgals3‐KO mice having an increased response, contrasting with our earlier study. These notable sex differences suggest a potential role for sex hormones, most likely androgen signaling, being involved. In summary, our results suggest that targeting extracellular Gal‐3 function may be a suitable treatment for age‐related loss of bone mass.https://doi.org/10.1002/2211-5463.13483bone μCTCRISPR/Cas9galectingenetic animal modelssexual dimorphism |
| spellingShingle | Kevin A. Maupin Cassandra R. Diegel Payton D. Stevens Daniel Dick VAI Vivarium and Transgenic Core Bart O. Williams Mutation of the galectin‐3 glycan‐binding domain (Lgals3‐R200S) enhances cortical bone expansion in male mice and trabecular bone mass in female mice FEBS Open Bio bone μCT CRISPR/Cas9 galectin genetic animal models sexual dimorphism |
| title | Mutation of the galectin‐3 glycan‐binding domain (Lgals3‐R200S) enhances cortical bone expansion in male mice and trabecular bone mass in female mice |
| title_full | Mutation of the galectin‐3 glycan‐binding domain (Lgals3‐R200S) enhances cortical bone expansion in male mice and trabecular bone mass in female mice |
| title_fullStr | Mutation of the galectin‐3 glycan‐binding domain (Lgals3‐R200S) enhances cortical bone expansion in male mice and trabecular bone mass in female mice |
| title_full_unstemmed | Mutation of the galectin‐3 glycan‐binding domain (Lgals3‐R200S) enhances cortical bone expansion in male mice and trabecular bone mass in female mice |
| title_short | Mutation of the galectin‐3 glycan‐binding domain (Lgals3‐R200S) enhances cortical bone expansion in male mice and trabecular bone mass in female mice |
| title_sort | mutation of the galectin 3 glycan binding domain lgals3 r200s enhances cortical bone expansion in male mice and trabecular bone mass in female mice |
| topic | bone μCT CRISPR/Cas9 galectin genetic animal models sexual dimorphism |
| url | https://doi.org/10.1002/2211-5463.13483 |
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