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Nanopharmaceuticals in Alveolar Bone and Periodontal Regeneration
Published in Harishkumar Madhyastha, Durgesh Nandini Chauhan, Nanopharmaceuticals in Regenerative Medicine, 2022
Mark A. Reynolds, Zeqing Zhao, Michael D. Weir, Tao Ma, Jin Liu, Hockin H. K. Xu, Abraham Schneider
These results were likely due to the following mechanisms. First, HPL contains a wide spectrum of growth factors that can promote the MSC proliferating rate (Altaie et al. 2016). These include VEGF, TGF, PDGF, FGF, and IGF (Altaie et al. 2016). However, high concentrations of HPL (21.25% HPL) appeared to inhibit cell proliferation. The latter suggests a differential dose response to one or more proteins in HPL (Chen et al. 2012, Lee et al. 2011). Negative feedback is a mechanism that can block activation of the incoming signalling pathway to prevent inappropriate cellular response to excessive extracellular signals (such as growth factors) (Perrimon and McMahon 1999). Second, regarding the factors in HPL, TGF, IGF, FGF, and PDGF have been shown to enhance the osteogenesis of MSCs (Xia et al. 2011). TGF induces osteogenesis by activating receptor-regulated Smads and initiating mitogen-activated protein kinase signalling cascade (Iwasaki et al. 2018). TGF can also increase the Runx2 expression (Iwasaki et al. 2018). Moreover, IGF can upregulate type I collagen transcription and stabilise β-catenin, which is essential for osteoblastogenesis (Giustina et al. 2008). FGF can activate Runx2 and upregulate the anabolic function of osteoblasts (Majidinia et al. 2018). Furthermore, PDGF can promote the osteogenic differentiation by activating the BMP-Smad1/5/8- Runx2/Osterix pathway (Majidinia et al. 2018).
Skeletal Mechanobiology
Published in Jiro Nagatomi, Eno Essien Ebong, Mechanobiology Handbook, 2018
Alesha B. Castillo, Christopher R. Jacobs
Once recruited to newly resorbed sites, osteoprogenitors differentiate into mature bone-forming osteoblasts (Figure 13.1c) via activation of several osteogenic signaling pathways. Of these, Wnt signaling is critical at all stages of skeletal maintenance.18 Wnts are secreted glycoproteins that bind a receptor complex comprised of a seven-pass transmembrane protein, frizzled (Fz), and a single pass transmembrane protein of the low-density lipoprotein (LDL) receptor-related protein (LRP) family.19 Canonical Wnt signaling involves several proteins, including dishevelled (Dsh), axin, adenomatous polyposis coli (APC), glycogen synthase kinase (GSK)-3β, and β-catenin. β-catenin is a cytoplasmic phosphoprotein, which, in the absence of Wnt signaling, is targeted for degradation through phosphorylation by GSK-3β. However, upon Wnt binding, Dsh is phosphorylated leading to the phosphorylation and inactivation of GSK-3β, allowing β-catenin to accumulate in the cytoplasm. Subsequently, β-catenin translocates to the nucleus where it interacts with the T-cell and lymphoid enhancer (TCF-LEF) transcription factors to affect gene transcription.19 Target genes include Runx220 and Osterix,21 both of which are osteoblast-specific transcription factors critical in osteoblast differentiation, proliferation, activity, and apoptosis.22 Wnt signaling is inhibited by several proteins including sclerostin, which is encoded by the gene sclerosteosis (SOST),23 dickkopf1 (Dkk1),24 secreted frizzled-related protein 1 (sFRP1),25 and Wise.26 Thus, osteoblast differentiation is regulated by the spatial and temporal expression of Wnt-signaling modulators.
Biomimetic sponge using duck’s feet derived collagen and hydroxyapatite to promote bone regeneration
Published in Journal of Biomaterials Science, Polymer Edition, 2022
Jeong Eun Song, Dae Hoon Lee, Joo Hee Choi, Seong Won Lee, Gilson Khang, Sun-Jung Yoon
Runx2 is responsible for inducing the differentiation of multipotent mesenchymal cells into immature osteoblasts and activating several essential downstream proteins that maintain osteoblast differentiation and bone matrix genes [30]. BMSCs seeded into collagen sponges expressed Runx2 for 28 days. The 3% DC, 2% DC/HAp, and 3% DC/HAp sponges expressed higher Runx2 mRNA levels than the 2% DC sponge. The 2% DC/HAp sponge showed the highest Runx2 level, statistically significant. This result indicated that the collagen sponge used in this study had an osteoinductive effect on BMSCs. Moreover, this differentiation potential showed strong BMSCs in in vitro 3 D culture of 2% DC/HAp sponge.
Preparation and evaluation of stingray skin collagen/oyster osteoinductive composite scaffolds
Published in Journal of Biomaterials Science, Polymer Edition, 2023
Yue Wu, Yingkun Fu, Hongfu Pan, Cong Chang, Ningjian Ao, Hui Xu, Zhengnan Zhang, Ping Hu, Riwang Li, Shuxia Duan, Yan Yan Li
We detected the expressions of osteogenesis-related genes OCN, COL-I and RUNX2 after co-culture of MC3T3-E1 cells with composite scaffolds by RT-PCR. OCN is the most specific gene during osteoblast differentiation. It is late-expressed in cell proliferation and reaches maximum expression during mineralization [65]. It can be seen from Figure 7B(a) that the MC3T3-E1 cells cultured on the scaffolds all expressed the OCN gene normally, and the relationship with the culture time was positively correlated. Furthermore, the expression of OCN genes was associated with OSP doping. Col-OSP6 composite scaffolds exhibited higher levels of OCN gene expression compared to Col scaffolds. The possible reason was that OSP contained one or more signaling molecules capable of activating osteogenic capacity. This is consistent with the findings of Lamghari et al. [34, 66]. COL-I is the most abundant form of collagen protein in the human body and an important component of the extracellular matrix of bone [67]. COL-I gene expression was shown in Figure 7B(b). From the figure, we can see that the expression of COL-I gene increased with the extension of culture time. Moreover, the expression of COL-I gene was also related to the OSP in the composite scaffolds, that is, the Col-OSP6 composite scaffolds containing OSP was more favorable for the expression of COL-I gene. RUNX2 is a master regulator of osteogenic gene expression and osteogenic differentiation. It has been reported in the literature that RUNX2 knockout mice do not exhibit osteogenic differentiation, suggesting that osteogenic differentiation is completely blocked in the absence of RUNX2 [68]. Figure 7B(c) showed the expression of RUNX2 gene in MC3T3-E1 cells cultured on the composite scaffolds. In the early stage of culture, the expression level of RUNX2 gene was low, but with the extension of time, the scaffold material showed higher expression of RUNX2 gene. We believed that the RUNX2 gene expression of the Col-OSP6 composite scaffolds was higher than that of the pure Col scaffolds. Possible reason was that OSP contained one or more signaling molecules that activated osteogenic ability, and these signaling molecules had an activating effect on the gene markers OCN, COL-I and RUNX2 of osteogenic differentiation.
Generation of bioactive nano-composite scaffold of nanobioglass/silk fibroin/carboxymethyl cellulose for bone tissue engineering
Published in Journal of Biomaterials Science, Polymer Edition, 2018
Runx2 and osteocalcin are well known markers for osteogenic differentiation of human mesenchymal stem cells and hence, the generated constructs were investigated for the expression of Runx2 and osteocalcin at the end of culture period. Runx2 is an osteoblast specific transcription factor that acts intracellularly and controls the expression of bone tissue specific genes such as osteocalcin [85]. The immunocytochemistry for Runx2 expression of hMSCs over constructs on day 7 and 14 (Figure 7) was examined through the confocal microscopy. As indicated in Figure 7(A), Runx2 was expressed by hMSCs seeded over SF/CMC/10nBG was higher than control. Also, Runx2 expression was decreased by day 14 over both the scaffold, which indicates the differentiation of hMSCs towards osteogenic lineages through Runx2 dependent pathway [85]. As Runx2 is an early stage marker of osteogenic differentiation and observed to be well expressed by hMSCs cultured on nanofibrous composite scaffolds, we further measured the OCN expression, as it is an late marker that regulates the degree of mineralization [86]. Figure 7(B) depicts the higher expression of OCN over SF/CMC/10%nBG than control on day 7 and 14 of culture representing the enhanced hMSCs differentiation on bioglass loaded composite scaffold. The osteoblastic differentiation of hMSCs on the scaffolds was also assessed through integrated density measurement of Runx2 and osteocalcin expressions. On day 14 of culture, Figure 7(D) shows significantly (p < 0.05) higher level of OCN expression on SF/CMC/10%nBG in comparison to control. The Runx2 gene expression (Figure 7C) was observed to be lower on SF/CMC/10%nBG with significant difference after two weeks of culture, indicating the differentiation of hMSCs towards osteogenic lineage. Thus, the bioglass dissolution resulted into higher Si, Ca2+ and PO42− ion release through on exchange reaction, which triggers osteogenic differentiation and extracellular matrix mineralization of hMSCs over the construct generated by the recruitment and proliferation of hMSCs. Thereby, developed composite scaffold provided superior roughness, fibrous platform mimicking natural ECM, release of ions from silica rich layer and formation of apatite layer, which further prompted, attachment, spreading, proliferation and osteogenic differentiation of hMSCs.