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Is sonic Hedgehog involved in human fracture healing? --a prospective study on local and systemic concentrations of SHH.

Eipeldauer S, Thomas A, Hoechtl-Lee L, Kecht M, Binder H, Koettstorfer J, Gregori M, Sarahrudi K - PLoS ONE (2014)

Bottom Line: Evidence exist that SHH pathway plays a significant role in vasculogenesis and limb development during embryogenesis.A significant reduction of the SHH levels during the inflammatory phase of fracture healing was found.Further studies are definitely needed to clarify the underlying mechanisms.

View Article: PubMed Central - PubMed

Affiliation: University Clinic for Traumatology, Medical University of Vienna, Vienna, Austria.

ABSTRACT

Introduction: 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. 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.

Methods: Seventy-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.

Results: Fracture 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.

Conclusion: This 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.

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Related in: MedlinePlus

Comparison of the mean SHH concentrations between patient's serum (n = 69), control serum (n = 34) and fracture haemtoma (n = 16).
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pone-0114668-g001: Comparison of the mean SHH concentrations between patient's serum (n = 69), control serum (n = 34) and fracture haemtoma (n = 16).

Mentions: Local SHH concentration measured in fracture hematomas was higher than the systemic concentration measured at the same time in patient's serum but below the levels of control serum. The mean SHH concentration measured in the fracture hematoma was 2312,86±648,73 pg/ml and the mean SHH concentration in patients serum was 2090,38±319,50 pg/ml (p = 0.225). Mean SHH concentration in control serums was 2783,66±416,30 pg/ml. There were no significant differences between control serums and fracture haematomas (p<0.289), or patient's serum (p = 0,065). Fig. 1 demonstrates the local and serum SHH concentrations immediately after fracture.


Is sonic Hedgehog involved in human fracture healing? --a prospective study on local and systemic concentrations of SHH.

Eipeldauer S, Thomas A, Hoechtl-Lee L, Kecht M, Binder H, Koettstorfer J, Gregori M, Sarahrudi K - PLoS ONE (2014)

Comparison of the mean SHH concentrations between patient's serum (n = 69), control serum (n = 34) and fracture haemtoma (n = 16).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4263617&req=5

pone-0114668-g001: Comparison of the mean SHH concentrations between patient's serum (n = 69), control serum (n = 34) and fracture haemtoma (n = 16).
Mentions: Local SHH concentration measured in fracture hematomas was higher than the systemic concentration measured at the same time in patient's serum but below the levels of control serum. The mean SHH concentration measured in the fracture hematoma was 2312,86±648,73 pg/ml and the mean SHH concentration in patients serum was 2090,38±319,50 pg/ml (p = 0.225). Mean SHH concentration in control serums was 2783,66±416,30 pg/ml. There were no significant differences between control serums and fracture haematomas (p<0.289), or patient's serum (p = 0,065). Fig. 1 demonstrates the local and serum SHH concentrations immediately after fracture.

Bottom Line: Evidence exist that SHH pathway plays a significant role in vasculogenesis and limb development during embryogenesis.A significant reduction of the SHH levels during the inflammatory phase of fracture healing was found.Further studies are definitely needed to clarify the underlying mechanisms.

View Article: PubMed Central - PubMed

Affiliation: University Clinic for Traumatology, Medical University of Vienna, Vienna, Austria.

ABSTRACT

Introduction: 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. 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.

Methods: Seventy-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.

Results: Fracture 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.

Conclusion: This 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.

Show MeSH
Related in: MedlinePlus