Enhanced osteoblastic differentiation of parietal bone in a novel murine model of mucopolysaccharidosis type II
Mucopolysaccharidosis type II (MPS II, OMIM 309900) is an X-linked disorder caused by a deficiency of lysosomal enzyme iduronate-2-sulfatase (IDS). The clinical manifestations of MPS II involve cognitive decline, bone deformity, and visceral disorders. These manifestations are closely associated wit...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-12-01
|
| Series: | Molecular Genetics and Metabolism Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214426923000678 |
| _version_ | 1797526220413337600 |
|---|---|
| author | Narutoshi Yamazaki Mari Ohira Shuji Takada Akira Ohtake Masafumi Onodera Mahito Nakanishi Torayuki Okuyama Ryuichi Mashima |
| author_facet | Narutoshi Yamazaki Mari Ohira Shuji Takada Akira Ohtake Masafumi Onodera Mahito Nakanishi Torayuki Okuyama Ryuichi Mashima |
| author_sort | Narutoshi Yamazaki |
| collection | DOAJ |
| description | Mucopolysaccharidosis type II (MPS II, OMIM 309900) is an X-linked disorder caused by a deficiency of lysosomal enzyme iduronate-2-sulfatase (IDS). The clinical manifestations of MPS II involve cognitive decline, bone deformity, and visceral disorders. These manifestations are closely associated with IDS enzyme activity, which catalyzes the stepwise degradation of heparan sulfate and dermatan sulfate. In this study, we established a novel Ids-deficient mice and further assessed the enzyme's physiological role. Using DNA sequencing, we found a genomic modification of the Ids genome, which involved the deletion of a 138-bp fragment spanning from intron 2 to exon 3, along with the insertion of an adenine at the 5′ end of exon 3 in the mutated allele. Consistent with previous data, our Ids-deficient mice showed an attenuated enzyme activity and an enhanced accumulation of glycosaminoglycans. Interestingly, we noticed a distinct enlargement of the calvarial bone in both neonatal and young adult mice. Our examination revealed that Ids deficiency led to an enhanced osteoblastogenesis in the parietal bone, a posterior part of the calvarial bone originating from the paraxial mesoderm and associated with an enhanced expression of osteoblastic makers, such as Col1a and Runx2. In sharp contrast, cell proliferation of the parietal bone in these mice appeared similar to that of wild-type controls. These results suggest that the deficiency of Ids could be involved in an augmented differentiation of calvarial bone, which is often noticed as an enlarged head circumference in MPS II-affected individuals. |
| first_indexed | 2024-03-10T09:27:08Z |
| format | Article |
| id | doaj.art-eb24e9ce4dae491295f89c82b84acf30 |
| institution | Directory Open Access Journal |
| issn | 2214-4269 |
| language | English |
| last_indexed | 2024-03-10T09:27:08Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Genetics and Metabolism Reports |
| spelling | doaj.art-eb24e9ce4dae491295f89c82b84acf302023-11-22T04:47:33ZengElsevierMolecular Genetics and Metabolism Reports2214-42692023-12-0137101021Enhanced osteoblastic differentiation of parietal bone in a novel murine model of mucopolysaccharidosis type IINarutoshi Yamazaki0Mari Ohira1Shuji Takada2Akira Ohtake3Masafumi Onodera4Mahito Nakanishi5Torayuki Okuyama6Ryuichi Mashima7Department of Clinical Laboratory Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan; Department of Clinical Genomics, Faculty of Medicine, Saitama Medical University, Saitama 350-0495, Japan; Corresponding author at: Department of Clinical Laboratory Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan.Department of Clinical Laboratory Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, JapanDepartment of Systems BioMedicine, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, JapanDepartment of Clinical Genomics, Faculty of Medicine, Saitama Medical University, Saitama 350-0495, Japan; Center for Intractable Diseases, Saitama Medical University Hospital, Saitama 350-0495, JapanDepartment of Human Genetics, National Research Institute for Child Health and Development, Tokyo, JapanTOKIWA-Bio Inc., 2-1-6 Sengen, Tsukuba City, Ibaraki 305-0047, Japan.Department of Clinical Laboratory Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan; Department of Clinical Genomics, Faculty of Medicine, Saitama Medical University, Saitama 350-0495, JapanDepartment of Clinical Laboratory Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, JapanMucopolysaccharidosis type II (MPS II, OMIM 309900) is an X-linked disorder caused by a deficiency of lysosomal enzyme iduronate-2-sulfatase (IDS). The clinical manifestations of MPS II involve cognitive decline, bone deformity, and visceral disorders. These manifestations are closely associated with IDS enzyme activity, which catalyzes the stepwise degradation of heparan sulfate and dermatan sulfate. In this study, we established a novel Ids-deficient mice and further assessed the enzyme's physiological role. Using DNA sequencing, we found a genomic modification of the Ids genome, which involved the deletion of a 138-bp fragment spanning from intron 2 to exon 3, along with the insertion of an adenine at the 5′ end of exon 3 in the mutated allele. Consistent with previous data, our Ids-deficient mice showed an attenuated enzyme activity and an enhanced accumulation of glycosaminoglycans. Interestingly, we noticed a distinct enlargement of the calvarial bone in both neonatal and young adult mice. Our examination revealed that Ids deficiency led to an enhanced osteoblastogenesis in the parietal bone, a posterior part of the calvarial bone originating from the paraxial mesoderm and associated with an enhanced expression of osteoblastic makers, such as Col1a and Runx2. In sharp contrast, cell proliferation of the parietal bone in these mice appeared similar to that of wild-type controls. These results suggest that the deficiency of Ids could be involved in an augmented differentiation of calvarial bone, which is often noticed as an enlarged head circumference in MPS II-affected individuals.http://www.sciencedirect.com/science/article/pii/S2214426923000678Mucopolysaccharidosis IIHunter syndromeIduronate-2-sulfataseBone deformity |
| spellingShingle | Narutoshi Yamazaki Mari Ohira Shuji Takada Akira Ohtake Masafumi Onodera Mahito Nakanishi Torayuki Okuyama Ryuichi Mashima Enhanced osteoblastic differentiation of parietal bone in a novel murine model of mucopolysaccharidosis type II Molecular Genetics and Metabolism Reports Mucopolysaccharidosis II Hunter syndrome Iduronate-2-sulfatase Bone deformity |
| title | Enhanced osteoblastic differentiation of parietal bone in a novel murine model of mucopolysaccharidosis type II |
| title_full | Enhanced osteoblastic differentiation of parietal bone in a novel murine model of mucopolysaccharidosis type II |
| title_fullStr | Enhanced osteoblastic differentiation of parietal bone in a novel murine model of mucopolysaccharidosis type II |
| title_full_unstemmed | Enhanced osteoblastic differentiation of parietal bone in a novel murine model of mucopolysaccharidosis type II |
| title_short | Enhanced osteoblastic differentiation of parietal bone in a novel murine model of mucopolysaccharidosis type II |
| title_sort | enhanced osteoblastic differentiation of parietal bone in a novel murine model of mucopolysaccharidosis type ii |
| topic | Mucopolysaccharidosis II Hunter syndrome Iduronate-2-sulfatase Bone deformity |
| url | http://www.sciencedirect.com/science/article/pii/S2214426923000678 |
| work_keys_str_mv | AT narutoshiyamazaki enhancedosteoblasticdifferentiationofparietalboneinanovelmurinemodelofmucopolysaccharidosistypeii AT mariohira enhancedosteoblasticdifferentiationofparietalboneinanovelmurinemodelofmucopolysaccharidosistypeii AT shujitakada enhancedosteoblasticdifferentiationofparietalboneinanovelmurinemodelofmucopolysaccharidosistypeii AT akiraohtake enhancedosteoblasticdifferentiationofparietalboneinanovelmurinemodelofmucopolysaccharidosistypeii AT masafumionodera enhancedosteoblasticdifferentiationofparietalboneinanovelmurinemodelofmucopolysaccharidosistypeii AT mahitonakanishi enhancedosteoblasticdifferentiationofparietalboneinanovelmurinemodelofmucopolysaccharidosistypeii AT torayukiokuyama enhancedosteoblasticdifferentiationofparietalboneinanovelmurinemodelofmucopolysaccharidosistypeii AT ryuichimashima enhancedosteoblasticdifferentiationofparietalboneinanovelmurinemodelofmucopolysaccharidosistypeii |