Topical application of Heparanase-1 facilitates bone remodeling during the healing of bone defects in a mouse model
- PMID: 31985568
- DOI: 10.1097/JCMA.0000000000000261
Topical application of Heparanase-1 facilitates bone remodeling during the healing of bone defects in a mouse model
Abstract
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.
Comment in
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Healing.J Chin Med Assoc. 2020 Aug;83(8):695-696. doi: 10.1097/JCMA.0000000000000330. J Chin Med Assoc. 2020. PMID: 32332517 No abstract available.
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Heparanase-1 facilitates bone remodeling on bone defect animal model with optimal dosage and treatment duration.J Chin Med Assoc. 2020 Sep;83(9):799-800. doi: 10.1097/JCMA.0000000000000391. J Chin Med Assoc. 2020. PMID: 32649419 Free PMC article. No abstract available.
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Does exogenously adding heparanase accelerate bone healing?J Chin Med Assoc. 2020 Nov;83(11):975-976. doi: 10.1097/JCMA.0000000000000432. J Chin Med Assoc. 2020. PMID: 32947507 Free PMC article. No abstract available.
References
-
- Marsell R, Einhorn TA. The biology of fracture healing.Injury201142551–5
-
- Fazzalari NL. Bone fracture and bone fracture repair.Osteoporos Int2011222003–6
-
- Bishop JR, Schuksz M, Esko JD. Heparan sulphate proteoglycans fine-tune mammalian physiology.Nature20074461030–7
-
- Globus RK, Patterson-Buckendahl P, Gospodarowicz D. Regulation of bovine bone cell proliferation by fibroblast growth factor and transforming growth factor beta.Endocrinology198812398–105
-
- Street J, Bao M, deGuzman L, Bunting S, Peale FV Jr, Ferrara N, et al. Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover.Proc Natl Acad Sci U S A2002999656–61
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