Abstract
IntroductionSonic Hedgehog (SHH) is a new signalling pathway in bone repair. Evidence exist that SHH pathway plays a significant role in vasculogenesis and limb development during embryogenesis. Some in vitro and animal studies has already proven its potential for bone regeneration. However, no data on the role of SHH in the human fracture healing have been published so far.MethodsSeventy-five patients with long bone fractures were included into the study and divided in 2 groups. First group contained 69 patients with normal fracture healing. Four patients with impaired fracture healing formed the second group. 34 volunteers donated blood samples as control. Serum samples were collected over a period of 1 year following a standardized time schedule. In addition, SHH levels were measured in fracture haematoma and serum of 16 patients with bone fractures.ResultsFracture haematoma and patients serum both contained lower SHH concentrations compared to control serum. The comparison between the patients' serum SHH level and the control serum revealed lower levels for the patients at all measurement time points. Significantly lower concentrations were observed at weeks 1 and 2 after fracture. SHH levels were slightly decreased in patients with impaired fracture healing without statistical significance.ConclusionThis is the first study to report local and systemic concentration of SHH in human fracture healing and SHH serum levels in healthy adults. A significant reduction of the SHH levels during the inflammatory phase of fracture healing was found. SHH concentrations in fracture haematoma and serum were lower than the concentration in control serum for the rest of the healing period. Our findings indicate that there is no relevant involvement of SHH in human fracture healing. Fracture repair process seem to reduce the SHH level in human. Further studies are definitely needed to clarify the underlying mechanisms.
Highlights
Sonic Hedgehog (SHH) is a new signalling pathway in bone repair
Our findings indicate that there is no relevant involvement of SHH in human fracture
During the last 2 decades various studies on bone regeneration have concentrated their topics on different cytokines, angiogenic factors, proteases and growth factors such as TGF beta 1 VEGF, MCS-F and many more that were considered to be relevant for fracture healing [1,2,3,4,5,6,7,8,9,10,11,12,13]
Summary
Sonic Hedgehog (SHH) is a new signalling pathway in bone repair. Evidence exist that SHH pathway plays a significant role in vasculogenesis and limb development during embryogenesis. SHH levels were measured in fracture haematoma and serum of 16 patients with bone fractures. Results: Fracture haematoma and patients serum both contained lower SHH concentrations compared to control serum. SHH concentrations in fracture haematoma and serum were lower than the concentration in control serum for the rest of the healing period. A quite new and promising molecular signalling pathway in bone repair seems to be Sonic Hedgehog (SHH), a member of the Hedgehog family. It was first isolated in 1995 in the drosophila melanogaster. There is evidence from in vitro studies that SHH is involved in the bone regeneration process in adults and initiates osteoblastic differentiation during endochondral bone formation. [16, 20]
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