Strontium-containing apatite/polylactide composites enhance bone formation in osteopenic rabbits

Strontium (Sr) has been shown to favor bone formation and is used clinically to treat osteoporosis. We have previously reported that Sr addition in apatite/polylactide composites could enhance the BMP-induced bone formation around implants at ectopic site in healthy animals. In this study we aimed to investigate the effectiveness of Sr addition on the local bone formation in osteoporosis. Apatite/polylactide composite granules with different Sr content were loaded with equal amount of rhBMP-2 and implanted intramuscularly in healthy rabbits (Con) and rabbits that received bilateral ovariectomy and daily injection of glucocorticoid (OP) for 12 weeks. The potential effect of Sr on the final volume of BMP-induced bone in both groups was investigated histologically and histomorphometrically. The de novo bone formed in OP implants was significantly less than in Con group when the implants contained no Sr, indicating that the BMP-induced osteogenesis was impaired in OP animals. Sr substitution as low as 0.5 mol% in apatite increased the bone volume in OP implants to levels comparable to that in the Con group, indicating a positive effect of Sr addition on the local bone formation in OP animals. In addition, more adipose tissue formed in parallel with the appearance of cartilage tissue in OP implants, suggesting that the differentiation potential of stem cell in OP animals may have shifted towards adipogenesis and chondrogenesis. From these results, we conclude that the use of Sr addition to enhance the bone growth surrounding implants in osteoporosis merits further study. Statement of Significance The impaired bone healing capacity of osteoporotic patients might result in poor osteointegration and surgical failure in case implants are placed. In this study we aimed to enhance the bone formation around implants under such scenario by adding strontium as the stimulus. Different from other studies, the samples were loaded with rhBMP-2 and implanted at an ectopic site (spinal muscles of New Zealand rabbits) to exclude the influence of conductive bone repair. The results showed that the addition of strontium could enhance the BMP-2-induced bone formation on implants in osteopenic rabbits to levels comparable to that in healthy rabbits. Secondarily, we observed more adipose tissue and cartilage tissue in osteopenic implants, suggesting the role of adipogenesis and chondrogenesis in osteopenia/osteoporosis

Molecular Docking Characterization of a Four-Domain Segment of Human Fibronectin Encompassing the RGD Loop with Hydroxyapatite

Fibronectin adsorption on biomaterial surfaces plays a key role in the biocompatibility of biomedical implants. In the current study, the adsorption behavior of the 7–10th type III modules of fibronectin (FN-III7–10) in the presence of hydroxyapatite (HAP) was systematically investigated by using molecular docking approach. It was revealed that the FN-III10 is the most important module among FN-III7–10 in promoting fibronectin binding to HAP by optimizing the interaction energy; the arginine residues were observed to directly interact with the hydroxyl group of HAP through electrostatic forces and hydrogen bonding. Moreover, it was found that the HAP-binding sites on FN-III10 are mainly located at the RGD loop region, which does not affect the interaction between the fibronectin protein and its cognate receptors on the cell surface

Variation of the bone forming ability with the physicochemical properties of calcium phosphate bone substitutes

Because of their bioactive properties and chemical similarity to the inorganic component of bone, calcium phosphate (CaP) materials are widely used for bone regeneration. Six commercially available CaP bone substitutes (Bio-Oss, Actifuse, Bi-Ostetic, MBCP, Vitoss and chronOs) as well as two tricalcium phosphate (TCP) ceramics with either a micron-scale (TCP-B) or submicron-scale (TCP-S) surface structure are characterized and their bone forming potential is evaluated in a canine ectopic implantation model. After 12 weeks of implantation in the paraspinal muscle of four beagles, sporadic bone (0.1 ± 0.1%) is observed in two Actifuse implants (2/4), limited bone (2.1 ± 1.4%) in four MBCP implants (4/4) and abundant bone (21.6 ± 4.5%) is formed in all TCP-S implants (4/4). Bone is not observed in any of the Bio-Oss, Bi-Ostetic, Vitoss, chronOs and TCP-B implants (0/4). When correlating the bone forming potential with the physicochemical properties of each material, we observe that the physical characteristics (e.g. grain size and micropore size at the submicron scale) might be the dominant trigger of material directed bone formation via specific mechanotransduction, instead of protein adsorption, surface mineralization and calcium ion release

Lin28 affects the proliferation and osteogenic differentiation of human dental pulp stem cells by directly inhibiting let-7b maturation

Abstract Objective Activation of Lin28 gene under certain conditions promotes tissue damage repair. However, it remains unknown whether conditional expression of Lin28 facilitates the recovery of damaged pulp tissue. In the study, we focus on exploring the effects and possible regulatory mechanisms of Lin28 on the proliferation and differentiation of human dental pulp stem cells (hDPSCs). Materials and methods We adopted techniques such as the ethynyl-2ʹ-deoxyuridine (EdU) incorporation assay, RNA-protein immunoprecipitation (RIP) analysis, and luciferase assays to study the regulation of hDPSCs by Lin28. Furthermore, gain-of-function and loss-of-function analyses were also used in explored factors regulating hDPSCs activation. Results The results show that Lin28 inhibited osteogenic differentiation by directly targets pre-let-7b. Through bioinformatics sequencing and dual luciferase experiments we learned that let-7b directly targets the IGF2BP2 3’UTR. Silencing of IGF2BP2 showed a similar biological effect as overexpression of let-7b. Overexpression of IGF2BP2 counteracted the differentiation-promoting effects produced by let-7b overexpression. Discussion/conclusions In conclusion, the RNA-binding protein Lin28 regulates osteogenic differentiation of hDPSCs by inhibiting let-7 miRNA maturation. And mature let-7b directly regulated the expression of IGF2BP2 by targeting the 3’UTR region of IGF2BP2 mRNA thus further inhibiting the differentiation of hDPSCs