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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

SHH serum concentrations (mean ± SEM) of patients with long-bone fractures and impaired bone healing after initial fixation for fracture (non-union) (n = 4) and the same patients after re-operation for non-union (non-union after reop.) (n = 4).
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pone-0114668-g003: SHH serum concentrations (mean ± SEM) of patients with long-bone fractures and impaired bone healing after initial fixation for fracture (non-union) (n = 4) and the same patients after re-operation for non-union (non-union after reop.) (n = 4).

Mentions: Only 4 patients had a complete data set and were subsequently included in this analysis. All 4 patients underwent reoperation for non-union, and consequently achieved proper bony consolidation and healed after the revision surgery. After surgical intervention for non-union, serum concentrations decreased rapidly at 1 week to reach its minimum at week 2 (1404±363 pg/ml). This was then followed by a constant, clear increase until week 8 after reoperation (2225,33±154,09 pg/ml). The concentrations decreased again at week 12 (1642.33±221.9 pg/l). Fig. 3 demonstrates the mean SHH concentrations of the patients with impaired healing before and after re-operation for non-union.


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)

SHH serum concentrations (mean ± SEM) of patients with long-bone fractures and impaired bone healing after initial fixation for fracture (non-union) (n = 4) and the same patients after re-operation for non-union (non-union after reop.) (n = 4).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0114668-g003: SHH serum concentrations (mean ± SEM) of patients with long-bone fractures and impaired bone healing after initial fixation for fracture (non-union) (n = 4) and the same patients after re-operation for non-union (non-union after reop.) (n = 4).
Mentions: Only 4 patients had a complete data set and were subsequently included in this analysis. All 4 patients underwent reoperation for non-union, and consequently achieved proper bony consolidation and healed after the revision surgery. After surgical intervention for non-union, serum concentrations decreased rapidly at 1 week to reach its minimum at week 2 (1404±363 pg/ml). This was then followed by a constant, clear increase until week 8 after reoperation (2225,33±154,09 pg/ml). The concentrations decreased again at week 12 (1642.33±221.9 pg/l). Fig. 3 demonstrates the mean SHH concentrations of the patients with impaired healing before and after re-operation for non-union.

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