ECTS2016 Poster Presentations Bone development/growth and fracture repair (35 abstracts)
Sulfated hyaluronan improves bone defect healing in type 2 diabetic rats by increasing osteoblast function
Ann-Kristin Picke 1 , Juliane Salbach-Hirsch 1 , Vera Hintze 2 , Martina Rauner 1 , Stephanie Möller 3 , Christian Kascholke 4 , Michael C Hacker 4 , Michaela Schulz-Siegmund 4 , Matthias Schnabelrauch 3 , Dieter Scharnweber 2, , Lorenz C Hofbauer 1, & Christine Hofbauer 6
1Division of Endocrinology, Diabetes, and Metabolic Bone Diseases, Department of Medicine III, Technische Universität Dresden, Dresden, Germany; 2Institute of Materials Science, Max Bergmann Center of Biomaterials, Technische Universität Dresden, Dresden, Germany; 3Biomaterials Department, INNOVENT e.V., Jena, Germany; 4Institute of Pharmacy, Pharmaceutical Technology, University Leipzig, Leipzig, Germany; 5Center of Regenerative Therapies Dresden, Dresden, Germany; 6University Center of Orthopeadics and Traumatology, University Medicine Carl Gustav Carus Dresden, Dresden, Germany.
Bone fractures of patients suffering from type 2 diabetes mellitus (T2DM) represent an emerging socioeconomic problem. Underling mechanisms are poorly understood and therapies are limited. Our previous studies have shown that sulfated hyaluronan (sHA3) suppresses osteoclast activity while supporting osteoblast function in vitro. Hence, we now investigated if sHA3 can improve the delayed fracture healing in rats with T2DM.
Porous, cross-linked lactide-based (TriLA) scaffolds were coated with collagen-based matrices including sHA3 and inserted into a subcritical femoral gap defect in non-diabetic (+/+) and diabetic (fa/fa) Zucker Diabetic Fatty (ZDF) rats. After 12 weeks, bone regeneration was assessed using μCT and histology.
As expected, diabetic ZDF rats displayed a delayed bone defect healing compared to non-diabetic controls. After 12 weeks, TriLA scaffolds showed no systemic effects except for an elevated P1NP serum concentration (+31%) in diabetic rats. The bone defect filling in T2DM increased to the level of non-diabetic control rats (with pure collagen-coating) after collagen/sHA3-coating. On the histological level, the mineralization amount increased with sHA3 (+/+:+336%, fa/fa: +151%) whereas the amount of osteoid decreased in both genotypes (+/+: −86%, fa/fa: −75%). Osteoblast-like UMR-106 and osteoclast-like RAW-264.7 cells were incubated with sHA3 and increasing glucose concentrations (40 and 100 mM). After sHA3, osteoblasts had less cell death events, while high glucose had no effect. The gene expression level of BMP2 increased (up to +182%), while the RANKL/OPG ratio decreased by −72%. The expression of osteoclast differentiation markers (NFATc1, TRAP, OSCAR) were reduced after sHA3 incubation and high glucose further decreased their expression while cell death events were diminished.
We showed that the collagen/sHA3 coating of TriLA scaffolds improved the defect filling in diabetic rats by supporting bone mineralization. Possibly, a decreased osteoclast differentiation due to osteogenic and anti-osteoclastic effects of osteoblasts may represent underlying mechanisms.
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Bone Abstracts
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