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Enzyme replacement therapy in mice lacking arylsulfatase B targets bone-remodeling cells, but not chondrocytes
- Source :
- Human Molecular Genetics, Human molecular genetics
- Publication Year :
- 2020
- Publisher :
- Oxford University Press (OUP), 2020.
-
Abstract
- Mucopolysaccharidosis type VI (MPS-VI), caused by mutational inactivation of the glycosaminoglycan-degrading enzyme arylsulfatase B (Arsb), is a lysosomal storage disorder primarily affecting the skeleton. We have previously reported that Arsb-deficient mice display high trabecular bone mass and impaired skeletal growth. In the present study, we treated them by weekly injection of recombinant human ARSB (rhARSB) to analyze the impact of enzyme replacement therapy (ERT) on skeletal growth and bone remodeling. We found that all bone-remodeling abnormalities of Arsb-deficient mice were prevented by ERT, whereas chondrocyte defects were not. Likewise, histologic analysis of the surgically removed femoral head from an ERT-treated MPS-VI patient revealed that only chondrocytes were pathologically affected. Remarkably, a side-by-side comparison with other cell types demonstrated that chondrocytes have substantially reduced capacity to endocytose rhARSB, together with low expression of the mannose receptor. We finally took advantage of Arsb-deficient mice to establish quantification of chondroitin sulfation for treatment monitoring. Our data demonstrate that bone-remodeling cell types are accessible to systemically delivered rhARSB, whereas the uptake into chondrocytes is inefficient. ispartof: HUMAN MOLECULAR GENETICS vol:29 issue:5 pages:803-816 ispartof: location:England status: published
- Subjects :
- Male
0301 basic medicine
Arylsulfatase B
N-Acetylgalactosamine-4-Sulfatase
Mucopolysaccharidosis type VI
PHENOTYPE
Bone remodeling
Mice
chemistry.chemical_compound
0302 clinical medicine
Genetics (clinical)
Mice, Knockout
Genetics & Heredity
Mucopolysaccharidosis IV
Mucopolysaccharidosis VI
MOUSE MODEL
General Medicine
Enzyme replacement therapy
Middle Aged
General Article Two
3. Good health
Chemistry
medicine.anatomical_structure
GROWTH
Female
Bone Remodeling
Life Sciences & Biomedicine
Mannose receptor
Adult
Biochemistry & Molecular Biology
medicine.medical_specialty
Adolescent
DISORDERS
Biology
DIAGNOSIS
Chondrocyte
Young Adult
03 medical and health sciences
Chondrocytes
Internal medicine
Genetics
medicine
Animals
Humans
Chondroitin
Enzyme Replacement Therapy
Molecular Biology
Science & Technology
RECEPTOR
Mice, Inbred C57BL
030104 developmental biology
Endocrinology
chemistry
VI
Human medicine
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 14602083 and 09646906
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- Human Molecular Genetics
- Accession number :
- edsair.doi.dedup.....6847d1589d908e09590bcc0a42e8677f