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Heparanase in primary human osteoblasts
Author(s) -
Smith Paul N.,
Freeman Craig,
Yu Di,
Chen Mingming,
Gatenby Paul A.,
Parish Christopher R.,
Li Rachel W.
Publication year - 2010
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.21138
Subject(s) - heparanase , downregulation and upregulation , osteoblast , bone remodeling , microbiology and biotechnology , osteoporosis , histone , chemistry , cancer research , gene expression , medicine , endocrinology , glycosaminoglycan , biology , gene , biochemistry , heparan sulfate , in vitro
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. 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. Published by Wiley Periodicals, Inc. J Orthop Res 28:1315–1322, 2010