TY - JOUR
T1 - Topical application of Heparanase-1 facilitates bone remodeling during the healing of bone defects in a mouse model
AU - Chiu, Po-Yu
AU - HuangFu, Wei-Chun
AU - Liu, I-Hsuan
AU - Chang, Ya-Pei
N1 - Funding Information:
The authors would like to thank Dr. Shau-Ping Lin for the assistance on the development of this project, Ms. Kai-Han Lin and Ms.Ke-Hsuan Wei for heparanase preparation,and Ms.Yen-Hua Lee and Dr. Chun-Chun Cheng for technical support on animal handling. We also thank the Taiwan Mouse Clinic (102-2325-B-001-042) which is funded by the National Research Program for Biopharmaceuticals (NRPB) at the Ministry of Science and Technology (MOST) of Taiwan for technical support in the acquisition and analysis of the micro-computed tomographic (µCT) data. This work was funded by Ministry of Science and Technology, Taiwan to I-Hsuan Liu (100-2313-B-002-052-MY2, 105-2628-B-002-005-MY4), Winston Teng-Kuei Cheng (102-2313-B-029-002), and Ya-Pei Chang (106-2313-B-002-041). The funding agency has no role in the experimental design, data acquirement, analysis, and interpretation of this work.
Publisher Copyright:
Copyright © 2020, the Chinese Medical Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
PY - 2020
Y1 - 2020
N2 - Background: Although previous studies have suggested a stimulatory role of heparanase in physiological bone turnover, the potential therapeutic role of heparanase in bone healing has not been elucidated. The purpose of this study was to assess the effect of topical application of heparanase-1 on bone healing. Methods: Two different dosages of recombinant mouse heparanase-1 and vehicle control were prepared and delivered via an osmotic pump to provide continuous topical infusion of the therapeutic reagent in a mouse bone defect model at the distal femoral metaphysis. The bone healing progress was evaluated by micro-computed tomography and histological examination at 7, 14, and 21 days after the bone defect was created. Results: The peak of trabecular bone generation was achieved earlier than anticipated with the use of heparanase as measured by medullary bone volume fraction and trabecular number observed in micro-computed tomography, while the remodeling of trabecular bone to cortical bone was also achieved earlier than anticipated with the use of heparanase as measured by connectivity density. Histopathological observation revealed a higher frequency of the presence of cartilaginous tissue in the heparanase-treated groups. Both bone mineral density and cortical bone volume fraction showed the best healing outcome with low-dose heparanase, implying a biphasic effect of its mode of action. Conclusion: These results indicated that with the appropriate dose of topical heparanase-1, the progress of bone healing could be accelerated in vivo.
AB - Background: Although previous studies have suggested a stimulatory role of heparanase in physiological bone turnover, the potential therapeutic role of heparanase in bone healing has not been elucidated. The purpose of this study was to assess the effect of topical application of heparanase-1 on bone healing. Methods: Two different dosages of recombinant mouse heparanase-1 and vehicle control were prepared and delivered via an osmotic pump to provide continuous topical infusion of the therapeutic reagent in a mouse bone defect model at the distal femoral metaphysis. The bone healing progress was evaluated by micro-computed tomography and histological examination at 7, 14, and 21 days after the bone defect was created. Results: The peak of trabecular bone generation was achieved earlier than anticipated with the use of heparanase as measured by medullary bone volume fraction and trabecular number observed in micro-computed tomography, while the remodeling of trabecular bone to cortical bone was also achieved earlier than anticipated with the use of heparanase as measured by connectivity density. Histopathological observation revealed a higher frequency of the presence of cartilaginous tissue in the heparanase-treated groups. Both bone mineral density and cortical bone volume fraction showed the best healing outcome with low-dose heparanase, implying a biphasic effect of its mode of action. Conclusion: These results indicated that with the appropriate dose of topical heparanase-1, the progress of bone healing could be accelerated in vivo.
KW - Bone regeneration
KW - Heparan sulfate
KW - Heparanase
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U2 - 10.1097/JCMA.0000000000000261
DO - 10.1097/JCMA.0000000000000261
M3 - Article
C2 - 31985568
SN - 1726-4901
VL - 83
SP - 272
EP - 279
JO - Journal of the Chinese Medical Association : JCMA
JF - Journal of the Chinese Medical Association : JCMA
IS - 3
ER -