Limits...
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.

Show MeSH

Related in: MedlinePlus

SHH serum concentrations (mean ± SEM) in controls (n = 34) and in patients with long-bone fractures and physiological healing (n = 69).Asterisks indicate significant differences in SHHconcentrations between patients and controls.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4263617&req=5

pone-0114668-g002: SHH serum concentrations (mean ± SEM) in controls (n = 34) and in patients with long-bone fractures and physiological healing (n = 69).Asterisks indicate significant differences in SHHconcentrations between patients and controls.

Mentions: Mean serum SHH concentrations were 2090,38±319,50 pg/ml immediately after fracture. Thereafter, the time course of SHH serum concentration was characterized by a continuous increase of the SHH levels until the 12th week. The mean SHH serum level was 2091,73±147,13 pg/ml at 1 week after fracture. Week 2 was characterized by a decrease of the SHH level (1884,86 pg/ml). Serum levels then again increased to peak at 12 weeks after trauma (2601,09±280,99 pg/ml). The concentrations decreased thereafter and reached 2399±181,54 pg/ml at 48 weeks after fracture. The comparison between the patients' SHH level and the control serum revealed lower levels for the patients at all measurement time points (Fig. 2). Significantly lower concentrations were observed at weeks 1 and 2 after fracture (week 1 p = 0.028, week 2 p = 0.016).


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) in controls (n = 34) and in patients with long-bone fractures and physiological healing (n = 69).Asterisks indicate significant differences in SHHconcentrations between patients and controls.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0114668-g002: SHH serum concentrations (mean ± SEM) in controls (n = 34) and in patients with long-bone fractures and physiological healing (n = 69).Asterisks indicate significant differences in SHHconcentrations between patients and controls.
Mentions: Mean serum SHH concentrations were 2090,38±319,50 pg/ml immediately after fracture. Thereafter, the time course of SHH serum concentration was characterized by a continuous increase of the SHH levels until the 12th week. The mean SHH serum level was 2091,73±147,13 pg/ml at 1 week after fracture. Week 2 was characterized by a decrease of the SHH level (1884,86 pg/ml). Serum levels then again increased to peak at 12 weeks after trauma (2601,09±280,99 pg/ml). The concentrations decreased thereafter and reached 2399±181,54 pg/ml at 48 weeks after fracture. The comparison between the patients' SHH level and the control serum revealed lower levels for the patients at all measurement time points (Fig. 2). Significantly lower concentrations were observed at weeks 1 and 2 after fracture (week 1 p = 0.028, week 2 p = 0.016).

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