Heparanase in Primary Human Osteoblasts

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 level of HSPE 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 hone turnover marker Gene profile studies demonstrated that osteogeme genes were downregulated in osteoporolic 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-mechated osteoblastogenesis through regulation of osteogen ic gene expression and htstone H3 modification HPSE upregulation may be a novel therapeutic approach in the prevention and treatment of (C) 2010 Orthopaedic Research Society Published by Wiley Periodicals, Inc J Orthop Res 28 1315-1322, 2010