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Beta-hexosaminidase subunit beta precursor (EC (Beta-N-acetylhexosaminidase subunit beta) (Hexosaminidase subunit B) (Cervical cancer proto-oncogene 7 protein) (HCC-7) (N-acetyl-beta-glucosaminidase subunit beta) [Contains: Beta-hexosaminidase subunit beta chain B; Beta-hexosaminidase subunit beta chain A] [HCC7]


Gene expression profiling suggests a pathological role of human bone marrow-derived mesenchymal stem cells in aging-related skeletal diseases.

Aging is associated with bone loss and degenerative joint diseases, in which the aging of bone marrow-derived mesenchymal stem cell (bmMSC)[1] may play an important role. In this study, we analyzed the gene expression profiles of bmMSC from 14 donors between 36 and 74 years old, and obtained age-associated genes (in the background of osteoarthritis) and osteoarthritis-associated genes (in the background of old age). Pathway analysis of these genes suggests that alterations in glycobiology might play an important role in the aging of human bmMSC. On the other hand, antigen presentation and signaling of immune cells were the top pathways enriched by osteoarthritis-associated genes, suggesting that alteration in immunology of bmMSC might be involved in the pathogenesis of osteoarthritis. Most intriguingly, we found significant age-associated differential expression of HEXA, HEXB, CTSK, SULF1, ADAMTS5, SPP1, COL8A2, GPNMB, TNFAIP6, and RPL29; those genes have been implicated in the bone loss and the pathology of osteoporosis and osteoarthritis in aging. Collectively, our results suggest a pathological role of bmMSC in aging-related skeletal diseases, and suggest the possibility that alteration in the immunology of bmMSC might also play an important role in the etiology of adult-onset osteoarthritis.

MeSH Terms

  • Adult
  • Aged
  • Aging
  • Animals
  • Bone Marrow Cells
  • Carbohydrate Conformation
  • Carbohydrate Sequence
  • Female
  • Gene Expression Profiling
  • Humans
  • Joint Diseases
  • Male
  • Mesenchymal Stem Cells
  • Middle Aged
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis
  • Osteoarthritis
  • Polysaccharides
  • Rats

Delayed symptom onset and increased life expectancy in Sandhoff disease mice treated with N-butyldeoxynojirimycin.

Sandhoff disease is a neurodegenerative disorder resulting from the autosomal recessive inheritance of mutations in the HEXB gene, which encodes the beta-subunit of beta-hexosaminidase. GM2 ganglioside fails to be degraded and accumulates within lysosomes in cells of the periphery and the central nervous system (CNS). There are currently no therapies for the glycosphingolipid lysosomal storage diseases that involve CNS pathology, including the GM2 gangliosidoses. One strategy for treating this and related diseases is substrate deprivation. This would utilize an inhibitor of glycosphingolipid biosynthesis to balance synthesis with the impaired rate of catabolism, thus preventing storage. One such inhibitor is N-butyldeoxynojirimycin, which currently is in clinical trials for the potential treatment of type 1 Gaucher disease, a related disease that involves glycosphingolipid storage in peripheral tissues, but not in the CNS. In this study, we have evaluated whether this drug also could be applied to the treatment of diseases with CNS storage and pathology. We therefore have treated a mouse model of Sandhoff disease with the inhibitor N-butyldeoxynojirimycin. The treated mice have delayed symptom onset, reduced storage in the brain and peripheral tissues, and increased life expectancy. Substrate deprivation therefore offers a potentially general therapy for this family of lysosomal storage diseases, including those with CNS disease.

MeSH Terms

  • 1-Deoxynojirimycin
  • Aging
  • Animals
  • Apoptosis
  • Behavior, Animal
  • Brain
  • Dentate Gyrus
  • Enzyme Inhibitors
  • Female
  • Genes, Recessive
  • Glycoside Hydrolase Inhibitors
  • Glycosphingolipids
  • Hexosaminidase B
  • Life Expectancy
  • Liver
  • Mice
  • Mice, Mutant Strains
  • Motor Activity
  • Sandhoff Disease
  • beta-N-Acetylhexosaminidases