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Heparanase in Primary Human Osteoblasts

Smith, Paul; Freeman, Craig; Yu, Di; Chen, Ming-Ming; Gatenby, Paul; Li, Rachel; Parish, Christopher

Description

Heparanase (HPSE) is known to be involved in fracture repair in mice, but its presence and function in human bone formation remains unclear. Our aim was to determine the expression of HPSE in human bone forming osteoblasts and to better understand its role in osteogenesis. HPSE protein expression and enzymatic activity were demonstrated in osteoblasts isolated from trabecular bone specimens of patients with osteoporosis (OP) and from healthy subjects, although the levels differed markedly....[Show more]

dc.contributor.authorSmith, Paul
dc.contributor.authorFreeman, Craig
dc.contributor.authorYu, Di
dc.contributor.authorChen, Ming-Ming
dc.contributor.authorGatenby, Paul
dc.contributor.authorLi, Rachel
dc.contributor.authorParish, Christopher
dc.date.accessioned2015-12-08T22:39:56Z
dc.identifier.issn0736-0266
dc.identifier.urihttp://hdl.handle.net/1885/36288
dc.description.abstractHeparanase (HPSE) is known to be involved in fracture repair in mice, but its presence and function in human bone formation remains unclear. Our aim was to determine the expression of HPSE in human bone forming osteoblasts and to better understand its role in osteogenesis. HPSE protein expression and enzymatic activity were demonstrated in osteoblasts isolated from trabecular bone specimens of patients with osteoporosis (OP) and from healthy subjects, although the levels differed markedly. Thus, low levels of HPSE expression were observed in osteoporotic osteoblasts, including in the nucleus compared to those from healthy subjects. Notably, HPSE gene expression was associated with alkaline phosphatase (ALP) activity, the bone turnover marker. Gene profile studies demonstrated that osteogenic genes were downregulated in osteoporotic osteoblasts. We further exposed osteoblasts to exogenous HPSE and found that the level of histone H3 phosphorylation was increased. We provide evidence, for the first time, demonstrating that HPSE expresses and functions in human osteoblasts. Our data suggest that previously undescribed function of HPSE-mediated osteoblastogenesis through regulation of osteogenic gene expression and histone H3 modification. HPSE upregulation may be a novel therapeutic approach in the prevention and treatment of OP.
dc.publisherElsevier
dc.sourceJournal of Orthopaedic Research
dc.subjectKeywords: alkaline phosphatase; heparanase; histone H3; adult; aged; article; bone development; bone turnover; cell structure; clinical article; controlled study; down regulation; enzyme activity; gene expression; human; human cell; osteoblast; osteoporosis; priori Extracellular matrix; Gene expression; Heparanase; Osteoblasts; Osteogenesis
dc.titleHeparanase in Primary Human Osteoblasts
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume28
dc.date.issued2010
local.identifier.absfor060199 - Biochemistry and Cell Biology not elsewhere classified
local.identifier.ariespublicationu6800332xPUB134
local.type.statusPublished Version
local.contributor.affiliationSmith, Paul, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationFreeman, Craig, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationYu, Di, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationChen, Ming-Ming, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationGatenby, Paul, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationParish, Christopher, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationLi, Rachel, College of Medicine, Biology and Environment, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.startpage1315
local.bibliographicCitation.lastpage1322
local.identifier.doi10.1002/jor.21138
local.identifier.absseo920116 - Skeletal System and Disorders (incl. Arthritis)
dc.date.updated2016-02-24T11:37:50Z
local.identifier.scopusID2-s2.0-77957194384
local.identifier.thomsonID000281657200008
CollectionsANU Research Publications

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