Expression of nerve growth factor in the callus during fracture healing in a fracture model in aged mice

2021 ◽  
pp. 1-7
Author(s):  
Hiroyuki Sekiguchi ◽  
Gen Inoue ◽  
Shintaro Shoji ◽  
Ryo Tazawa ◽  
Akiyoshi Kuroda ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Fracture Healing ◽  
Femur Fracture ◽  
Hypertrophic Chondrocytes ◽  
Nerve Growth ◽  
Expression Levels ◽  
Aged Mice ◽  
Chondrocyte Maturation ◽  
Young Mice

BACKGROUND: Impaired fracture healing results in extensive and prolonged disability and long-term pain. Previous studies reported that nerve growth factor (NGF) was expressed during fracture healing and that anti-NGF antibody improves physical activity associate with facture pain. However, NGF expression levels in delayed or non-union are not fully understood. OBJECTIVE: We compared chronological changes in NGF in the callus of young mice after femur fracture with those in aged mice after femur fracture as a model of bone fracture in the elderly. METHODS: We used young (age 8 weeks) and aged (age 10 months) male C57BL/6J mice. A fracture was generated in the femur. At 5, 7, 10, 14, 17, and 21 days after creation of a fracture, mRNA expression levels of Col2a1, Col10a1, NGF were evaluated using quantitative PCR. We examined NGF protein expression levels and localization in the callus at day 14 using ELISA and immunohistochemistry, respectively. RESULTS: Expression of NGF in the callus after femur fracture in aged mice was significantly greater than that in young mice at days 5, 7, 10, 17, and 21 days. NGF protein levels in the callus of aged mice were also significantly higher than that in young mice. Immunohistochemical staining showed that NGF was heavily expressed in hypertrophic chondrocytes in the callus in aged mice. CONCLUSIONS: It is suggested that delayed Col2a1 and Col10a1 expression reflects delayed chondrocyte formation and delayed chondrocyte maturation in aged mice and that higher NGF expression in aged mice at day 14 may be associated with the presence of remaining hypertrophic chondrocytes in callus with delaying endochondral ossification.

scholarly journals Effects of Exogenous Nerve Growth Factor on The Expression of BMP-9 and VEGF in The Healing of Rabbit Mandible Fracture With Local Nerve Injury

2020 ◽  
Author(s):  
Sen Yang ◽  
Jiao Cheng ◽  
Cheng Man ◽  
Lian Jiang ◽  
Guogeng Long ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Fracture Healing ◽  
Mandibular Fracture ◽  
Vascular Endothelial ◽  
Lower Lip ◽  
Nerve Growth ◽  
Qrt Pcr ◽  
Mandible Fracture ◽  
Mandible Fractures

Abstract Background: Mandibular fracture healing is a complex process involving nerves and growth factors. Nerve growth factor (NGF) not only facilitates the maintenance of sympathetic neurite growth but also stimulates other growth factors that can promote the essential osteogenesis and angiogenesis for fracture healing. Therefore, it is necessary to analyze the combined effects of NGF, bone morphogenic protein-9 (BMP-9), and vascular endothelial growth factor (VEGF) to accelerate the healing of mandible fractures.Methods: The models of mandible fracture with local nerve injury established in forty-eight rabbits were randomly divided into nerve growth factor group (NGF group), gelatin sponge group (GS group), blank group, and intact group. The recovery of nerve reflex was assessed by observing the number of rabbits with lower lip responses to acupuncture. The fracture healing was observed with visual and CBCT, and then callus tissues from the mandibular fracture area were collected for hematoxylin and eosin (HE) staining observation, and the expression of BMP-9 and VEGF in callus at different stages was detected by quantitative real-time PCR (qRT-PCR).Results: Needling reaction in the lower lip showed the number of animals with nerve reflex recovery was significantly higher in the NGF group than that in the GS and blank groups at the 2nd and 4th weeks after the operation. The combined results of macroscopic observation, CBCT examination, and histological analysis showed that a large number of osteoblasts and some vascular endothelial cells were found around the trabecular bone in the NGF group and the amount of callus formation and reconstruction was better than that in the GS group at the 2nd week after the operation. The qRT-PCR results indicated that the expression levels of BMP-9 and VEGF in the four groups reached the highest values at the 2nd week, while the expression levels of both in the NGF group were significantly higher than that in the GS group.Conclusion: The exogenous NGF could accelerate the healing of mandible fractures. This work will provide a new foundation and theoretical basis for clarifying the mechanism of fracture healing, thereby promoting fracture healing and reducing the disability rate of patients.

scholarly journals Effects of exogenous nerve growth factor on the expression of BMP-9 and VEGF in the healing of rabbit mandible fracture with local nerve injury

2020 ◽  
Author(s):  
Sen Yang ◽  
Jiao Cheng ◽  
Cheng Man ◽  
Lian Jiang ◽  
Guogeng Long ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Fracture Healing ◽  
Bone Growth ◽  
Mandibular Fracture ◽  
Vascular Endothelial ◽  
Nerve Growth ◽  
Mandible Fracture ◽  
Fracture Area ◽  
Endothelial Growth Factor

Abstract Background The fracture of mandible remains one of the most facial fractures and its healing is a complex process, involving nerve and growth factors. Currently, nerve growth factor not only benefits maintenance of sympathetic neurite growth, but also takes part in intricate regulatory network to stimulate other growth factors such as bone growth protein and vascular endothelial growth factor, which promote together essential osteogenesis and angiogenesis to physiological bone formation, growth and fracture healing. Therefore, it is necessary to analysis the combination of nerve growth factor, bone growth protein-9 and vascular endothelial growth factor to accelerate healing rate of mandible fracture. Methods The models of mandible fracture with local nerve injury established in forty-eight rabbits were randomly divided into nerve growth factor group (NGF group), gelatin sponge group (GS group), blank group and intact group with 12 rabbits in each group. The fracture healing was observed with visual and X-ray after the operation, then callus tissue in mandibular fracture area were collected for HE staining observation, and quantitative RT-PCR was used to detect the expression of BMP-9 and VEGF in callus at different stages. Results The combined results of macroscopic observation, X-ray examination and histological section showed that a large number of osteoblasts and some vascular endothelial cells were found around the trabecular bone in NGF group and the amount of callus formation and reconstruction were better than GS group at 2th weeks after the operation. Quantitative RT-PCR result indicated that the expression levels of BMP-9 mRNA and VEGF mRNA in the four groups reached the highest value at the second week, and then decreased with time. At the same time, the content of BMP-9 and VEGF in callus tissue in mandibular fracture area increased significantly in NGF group than GS group. Conclusion The exogenous NGF could improve the expressions of BMP-9 and VEGF in the early stage of mandibular fracture to accelerate healing of mandible fracture. This work provides a new foundation and theoretical basis to make clear mechanism of fracture healing, thereby promoting patients’ fracture healing and reducing their disability rate.

scholarly journals Effects of exogenous nerve growth factor on the expression of BMP-9 and VEGF in the healing of rabbit mandible fracture with local nerve injury

2020 ◽  
Author(s):  
Sen Yang ◽  
Jiao Cheng ◽  
Cheng Man ◽  
Lian Jiang ◽  
Guogeng Long ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Fracture Healing ◽  
Callus Tissue ◽  
Mandibular Fracture ◽  
Vascular Endothelial ◽  
Nerve Growth ◽  
X Ray ◽  
Mandible Fracture ◽  
Fracture Area

Abstract Background: The fracture of the mandible remains one of the most facial fractures and its healing is a complex process, involving nerve and growth factors. Currently, nerve growth factor not only benefits maintenance of sympathetic neurite growth but also takes part in the intricate regulatory network to stimulate other growth factors such as bone morphogenic protein (BMP) and vascular endothelial growth factor (VEGF), which promote together essential osteogenesis and angiogenesis to physiological bone formation, growth and fracture healing. Therefore, it is necessary to analyze the combination of nerve growth factor (NGF), bone morphogenic protein-9 (BMP-9), and VEGF to accelerate the healing rate of mandible fracture.Methods: The models of mandible fracture with local nerve injury established in forty-eight rabbits were randomly divided into nerve growth factor group (NGF group), gelatin sponge group (GS group), blank group, and intact group with 12 rabbits in each group. The fracture healing was observed with visual and X-ray after the operation, then callus tissue in the mandibular fracture area were collected for hematoxylin and eosin (HE) staining observation, and quantitative real-time PCR (qRT-PCR) was used to detect the expression of BMP-9 and VEGF in callus at different stages.Results: The combined results of macroscopic observation, X-ray examination, and histological section showed that a large number of osteoblasts and some vascular endothelial cells were found around the trabecular bone in the NGF group and the amount of callus formation and reconstruction was better than GS group at the 2nd weeks after the operation. QRT-PCR result indicated that the expression levels of BMP-9 mRNA and VEGF mRNA in the four groups reached the highest value at the 2nd week, and then decreased with time. At the same time, the content of BMP-9 and VEGF in callus tissue in the mandibular fracture area increased significantly in the NGF group than the GS group.Conclusion: The exogenous NGF could improve the expressions of BMP-9 and VEGF at the early stage of mandibular fracture to accelerate the healing of mandible fracture. This work will provide a new foundation and theoretical basis to make a clear mechanism of fracture healing, thereby promoting patients’ fracture healing and reducing their disability rate.

scholarly journals Effects of exogenous nerve growth factor on the expression of BMP-9 and VEGF in the healing of rabbit mandible fracture with local nerve injury

2020 ◽  
Author(s):  
Sen Yang ◽  
Jiao Cheng ◽  
Cheng Man ◽  
Lian Jiang ◽  
Guogeng Long ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Fracture Healing ◽  
Callus Tissue ◽  
Mandibular Fracture ◽  
Vascular Endothelial ◽  
Nerve Growth ◽  
X Ray ◽  
Mandible Fracture ◽  
Fracture Area

Abstract Background: The fracture of mandible remains one of the most facial fractures and its healing is a complex process, involving nerve and growth factors. Currently, nerve growth factor not only benefits maintenance of sympathetic neurite growth but also takes part in the intricate regulatory network to stimulate other growth factors such as bone morphogenic protein (BMP) and vascular endothelial growth factor (VEGF), which promote together essential osteogenesis and angiogenesis to physiological bone formation, growth and fracture healing. Therefore, it is necessary to analyze the combination of nerve growth factor (NGF), bone morphogenic protein-9 (BMP-9), and VEGF to accelerate the healing rate of mandible fracture.Methods: The models of mandible fracture with local nerve injury established in forty-eight rabbits were randomly divided into nerve growth factor group (NGF group), gelatin sponge group (GS group), blank group, and intact group with 12 rabbits in each group. The fracture healing was observed with visual and X-ray after the operation, then callus tissue in mandibular fracture area were collected for hematoxylin and eosin (HE) staining observation, and quantitative real-time PCR (qRT-PCR) was used to detect the expression of BMP-9 and VEGF in callus at different stages.Results: The combined results of macroscopic observation, X-ray examination, and histological section showed that a large number of osteoblasts and some vascular endothelial cells were found around the trabecular bone in the NGF group and the amount of callus formation and reconstruction was better than GS group at 2nd weeks after the operation. QRT-PCR result indicated that the expression levels of BMP-9 mRNA and VEGF mRNA in the four groups reached the highest value at 2nd week, and then decreased with time. At the same time, the content of BMP-9 and VEGF in callus tissue in the mandibular fracture area increased significantly in the NGF group than the GS group.Conclusion: The exogenous NGF could improve the expressions of BMP-9 and VEGF at the early stage of mandibular fracture to accelerate the healing of mandible fracture. This work will provide a new foundation and theoretical basis to make a clear mechanism of fracture healing, thereby promoting patients’ fracture healing and reducing their disability rate.

scholarly journals Effects of exogenous nerve growth factor on the expression of BMP-9 and VEGF in the healing of rabbit mandible fracture with local nerve injury

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Sen Yang ◽  
Jiao Cheng ◽  
Cheng Man ◽  
Lian Jiang ◽  
Guogeng Long ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Fracture Healing ◽  
Mandibular Fracture ◽  
Vascular Endothelial ◽  
Lower Lip ◽  
Nerve Growth ◽  
Qrt Pcr ◽  
Mandible Fracture ◽  
Mandible Fractures

Abstract Background Mandibular fracture healing is a complex process involving nerves and growth factors. Nerve growth factor (NGF) not only facilitates the maintenance of sympathetic neurite growth but also stimulates other growth factors that can promote the essential osteogenesis and angiogenesis for fracture healing. Therefore, it is necessary to analyze the combined effects of NGF, bone morphogenic protein-9 (BMP-9), and vascular endothelial growth factor (VEGF) to accelerate the healing of mandible fractures. Methods The models of mandible fracture with local nerve injury established in 48 rabbits were randomly divided into nerve growth factor group (NGF group), gelatin sponge group (GS group), blank group, and intact group. The recovery of nerve reflex was assessed by observing the number of rabbits with lower lip responses to acupuncture. The fracture healing was observed with visual and CBCT, and then callus tissues from the mandibular fracture area were collected for hematoxylin and eosin (HE) staining observation, and the expression of BMP-9 and VEGF in callus at different stages was detected by quantitative real-time PCR (qRT-PCR). Results Needling reaction in the lower lip showed the number of animals with nerve reflex recovery was significantly higher in the NGF group than that in the GS and blank groups at the 2nd and 4th weeks after the operation. The combined results of macroscopic observation, CBCT examination, and histological analysis showed that a large number of osteoblasts and some vascular endothelial cells were found around the trabecular bone in the NGF group and the amount of callus formation and reconstruction was better than that in the GS group at the 2nd week after the operation. The qRT-PCR results indicated that the expression levels of BMP-9 and VEGF in the four groups reached the highest values at the 2nd week, while the expression levels of both in the NGF group were significantly higher than that in the GS group. Conclusion The exogenous NGF could accelerate the healing of mandible fractures. This work will provide a new foundation and theoretical basis for clarifying the mechanism of fracture healing, thereby promoting fracture healing and reducing the disability rate of patients.

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