Strongly enhanced levels of sclerostin during human fracture healing

Department of Traumatology, Medical University of Vienna, Vienna, Austria.
Journal of Orthopaedic Research (Impact Factor: 2.97). 10/2012; 30(10):1549-55. DOI: 10.1002/jor.22129
Source: PubMed

ABSTRACT Sclerostin (SOST), an antagonist of Wnt signaling, is an important negative regulator of bone formation. However, no data on the role of SOST in the human fracture healing have been published so far. This study addressed this issue. Seventy-five patients with long bone fractures were included into the study and divided in two groups. The first group contained 69 patients with normal fracture healing. Six patients with impaired fracture healing formed the second group. Thirty-four volunteers donated blood samples as control. Serum samples were collected over a period of 1 year following a standardized time schedule. In addition, SOST levels were measured in fracture hematoma and serum of 16 patients with bone fractures. Fracture hematoma contained significantly higher SOST concentrations compared to patient's serum. SOST levels in fracture hematoma and in patient's serum were both significantly higher than in the serum of controls. Highly elevated SOST serum concentrations were found in patients with physiological fracture healing. SOST levels were decreased in patients with impaired fracture healing. However, this difference was not statistically significant. This is the first study to provide evidence of strongly enhanced SOST levels in patients with bone fracture. The results indicate local and systemic involvement of SOST in humans during fracture healing.

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    ABSTRACT: We investigated the influence of the osteocyte protein, sclerostin, on fracture healing by examining the dynamics and mechanisms of repair of single-cortex, stabilized femoral defects in sclerostin knockout (Sost(-/-); KO) and sclerostin wild-type (Sost(+/+); WT) mice. Fourteen days following generation of bone defects, Sost KO mice had significantly more bone in the healing defect than WT mice. The increase in regenerating bone was due to an increase in the thickness of trabecularized spicules, osteoblast numbers and surfaces within the defect. Enhanced healing of bone defects in Sost KO mice was associated with significantly more activated β-catenin expression than observed in WT mice. The findings were similar to those observed in Axin2(-/-) mice, in which β-catenin signaling is known to be enhanced to facilitate bone regeneration. Taken together, these data indicate that enhanced β-catenin signaling is present in Sost(-/-) mice that demonstrate accelerated healing of bone defects, suggesting that modulation of β-catenin signaling in bone could be used to promote fracture repair.
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