Pivotal roles of biglycan and decorin in regulating bone mass, water retention, and bone toughness
Abstract Proteoglycans, key components of non-collagenous proteins in the bone matrix, attract water through their negatively charged glycosaminoglycan chains. Among these proteoglycans, biglycan (Bgn) and decorin (Dcn) are major subtypes, yet their distinct roles in bone remain largely elusive. In...
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Nature Publishing Group
2025-01-01
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| Series: | Bone Research |
| Online Access: | https://doi.org/10.1038/s41413-024-00380-2 |
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| author | Rui Hua Yan Han Qingwen Ni Roberto J. Fajardo Renato V. Iozzo Rafay Ahmed Jeffry S. Nyman Xiaodu Wang Jean X. Jiang |
| author_facet | Rui Hua Yan Han Qingwen Ni Roberto J. Fajardo Renato V. Iozzo Rafay Ahmed Jeffry S. Nyman Xiaodu Wang Jean X. Jiang |
| author_sort | Rui Hua |
| collection | DOAJ |
| description | Abstract Proteoglycans, key components of non-collagenous proteins in the bone matrix, attract water through their negatively charged glycosaminoglycan chains. Among these proteoglycans, biglycan (Bgn) and decorin (Dcn) are major subtypes, yet their distinct roles in bone remain largely elusive. In this study, we utilized single knockout (KO) mouse models and successfully generated double KO (dKO) models despite challenges with low yield. Bgn deficiency, but not Dcn deficiency, decreased trabecular bone mass, with more pronounced bone loss in dKO mice. Low-field nuclear magnetic resonance measurements showed a marked decrease in bound water among all KO groups, especially in Bgn KO and dKO mice. Moreover, both Bgn KO and dKO mice exhibited reduced fracture toughness compared to Dcn KO mice. Dcn was significantly upregulated in Bgn KO mice, while a modest upregulation of Bgn was observed in Dcn KO mice, indicating Bgn’s predominant role in bone. High resolution atomic force microscopy showed decreased in situ permanent energy dissipation and increased elastic modulus in the extrafibrillar matrix of Bgn/Dcn deficient mice, which were diminished upon dehydration. Furthermore, we found that both Bgn and Dcn are indispensable for the activation of ERK and p38 MAPK signaling pathways. Collectively, our results highlight the distinct and indispensable roles of Bgn and Dcn in maintaining bone structure, water retention, and bulk/in situ tissue properties in the bone matrix, with Bgn exerting a predominant influence. |
| format | Article |
| id | doaj-art-566403c853744642ac56ca18b074b2e2 |
| institution | Kabale University |
| issn | 2095-6231 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Bone Research |
| spelling | doaj-art-566403c853744642ac56ca18b074b2e22025-01-05T12:11:11ZengNature Publishing GroupBone Research2095-62312025-01-0113111410.1038/s41413-024-00380-2Pivotal roles of biglycan and decorin in regulating bone mass, water retention, and bone toughnessRui Hua0Yan Han1Qingwen Ni2Roberto J. Fajardo3Renato V. Iozzo4Rafay Ahmed5Jeffry S. Nyman6Xiaodu Wang7Jean X. Jiang8Department of Biochemistry and Structural Biology, University of Texas Health Science CenterDepartment of Mechanical Engineering, University of Texas at San AntonioDepartment of Physics, Texas A&M International UniversitySchool of Osteopathic Medicine, University of the Incarnate WordDepartment of Pathology & Genomic Medicine, Sidney Kimmel Medical Collage, Thomas Jefferson UniversityDepartment of Orthopaedic Surgery, Vanderbilt University Medical CenterDepartment of Orthopaedic Surgery, Vanderbilt University Medical CenterDepartment of Mechanical Engineering, University of Texas at San AntonioDepartment of Biochemistry and Structural Biology, University of Texas Health Science CenterAbstract Proteoglycans, key components of non-collagenous proteins in the bone matrix, attract water through their negatively charged glycosaminoglycan chains. Among these proteoglycans, biglycan (Bgn) and decorin (Dcn) are major subtypes, yet their distinct roles in bone remain largely elusive. In this study, we utilized single knockout (KO) mouse models and successfully generated double KO (dKO) models despite challenges with low yield. Bgn deficiency, but not Dcn deficiency, decreased trabecular bone mass, with more pronounced bone loss in dKO mice. Low-field nuclear magnetic resonance measurements showed a marked decrease in bound water among all KO groups, especially in Bgn KO and dKO mice. Moreover, both Bgn KO and dKO mice exhibited reduced fracture toughness compared to Dcn KO mice. Dcn was significantly upregulated in Bgn KO mice, while a modest upregulation of Bgn was observed in Dcn KO mice, indicating Bgn’s predominant role in bone. High resolution atomic force microscopy showed decreased in situ permanent energy dissipation and increased elastic modulus in the extrafibrillar matrix of Bgn/Dcn deficient mice, which were diminished upon dehydration. Furthermore, we found that both Bgn and Dcn are indispensable for the activation of ERK and p38 MAPK signaling pathways. Collectively, our results highlight the distinct and indispensable roles of Bgn and Dcn in maintaining bone structure, water retention, and bulk/in situ tissue properties in the bone matrix, with Bgn exerting a predominant influence.https://doi.org/10.1038/s41413-024-00380-2 |
| spellingShingle | Rui Hua Yan Han Qingwen Ni Roberto J. Fajardo Renato V. Iozzo Rafay Ahmed Jeffry S. Nyman Xiaodu Wang Jean X. Jiang Pivotal roles of biglycan and decorin in regulating bone mass, water retention, and bone toughness Bone Research |
| title | Pivotal roles of biglycan and decorin in regulating bone mass, water retention, and bone toughness |
| title_full | Pivotal roles of biglycan and decorin in regulating bone mass, water retention, and bone toughness |
| title_fullStr | Pivotal roles of biglycan and decorin in regulating bone mass, water retention, and bone toughness |
| title_full_unstemmed | Pivotal roles of biglycan and decorin in regulating bone mass, water retention, and bone toughness |
| title_short | Pivotal roles of biglycan and decorin in regulating bone mass, water retention, and bone toughness |
| title_sort | pivotal roles of biglycan and decorin in regulating bone mass water retention and bone toughness |
| url | https://doi.org/10.1038/s41413-024-00380-2 |
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