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Stem Cell Engineering Using Bioactive Molecules for Bone-Regenerative Medicine
Published in Gilson Khang, Handbook of Intelligent Scaffolds for Tissue Engineering and Regenerative Medicine, 2017
Similar to others of the BMP family, BMP-4 is involved in bone and cartilage development. However, unlike other BMPs, it is also specifically involved in tooth development during the embryogenic stage. Therefore, Choi et al. identified and synthesized a peptide sequence corresponding to residues 15–24 of BMP-4, which are able to bind heparins (HBD, RKKNPNCRRH). The treatment of cultured human mesenchymal stem cells (hMSCs) with heparinase blocked both GAG chain detection and HBD peptide-induced osteogenic differentiation, while diminishing the increased phospho-ERK level. These results suggest that the discovered HBD stimulated osteoblastic differentiation via interactions with heparin and ERK signaling. In vivo results further demonstrated that HBD, as a mixed with an alginate gel, was able to induce bone formation in a bone defect71 (Fig. 44.4).
Tissue Engineering of Articular Cartilage
Published in Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi, Articular Cartilage, 2017
Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi
BMPs play a major role in endochondral bone formation and show general effects on cellular proliferation and matrix synthesis. As explained above, they are particularly attractive for cartilage engineering studies because they regulate both chondrogenesis and osteogenesis. Osteochondral integration is a critical factor in whether implants succeed or fail in vivo, so molecules that can stimulate this response are desirable (Pecina et al. 2002). As with TGF-β, BMPs can act synergistically with mechanical stimuli to accelerate regeneration of joint tissues. Currently, 20 types of BMPs have been identified, but only a subset has been examined for cartilage regeneration (Reddi 2003). BMPs generally have the ability to guide stem cells and immature bone and cartilage cells along the osteochondral pathway (O’Connor et al. 2000). BMP2 upregulated proteoglycan and collagen expression in chondrocytes (Gooch et al. 2002; Pecina et al. 2002; Valcourt et al. 2002), while also inducing better healing of defects in vivo (Frenkel et al. 2000; Pecina et al. 2002). BMP4 showed an ability to stimulate proteoglycan synthesis, bone formation, and cellular proliferation (Luyten et al. 1992; Pecina et al. 2002). BMP7 also showed positive effects on matrix synthesis (Pecina et al. 2002) and proliferation (Mattioli-Belmonte et al. 1999), while also decreasing type I collagen expression and suppressing infiltration of fibroblasts in vivo (Kaps et al. 2002). Articular chondrocytes treated with either BMP12 or 13 synthesized elevated levels of glycosaminoglycan, although these increases were less than that observed for cells treated with BMP2 (Gooch et al. 2002). Overall, experimental results have shown that BMPs have a generally positive effect on cartilage differentiation and morphogenesis, whether alone or in combination with other growth factors. For example, BMP2 application with IGF-1 resulted in more than onefold increases in aggregate modulus, accompanied by increases in glycosaminoglycan production, compared with controls (Elder and Athanasiou 2008).
Investigating orthodontic tooth movement: challenges and future directions
Published in Journal of the Royal Society of New Zealand, 2020
Fiona A. Firth, Rachel Farrar, Mauro Farella
Numerous studies have been performed by New Zealand researchers in which cultured PDL cells or osteoblasts have been mechanically loaded (Wescott et al. 2007; Pinkerton et al. 2008; Saminathan et al. 2012; Itskovich 2016; Firth 2017). Interestingly, a transient increase in apoptosis and expression of two apoptosis-related caspases (enzymes involved in programmed cell death and inflammation) has been detected in mechanically strained PDL cells in a two-dimensional (2D) culture, however the mechanism for this has not been identified (Wescott et al. 2007; Pinkerton et al. 2008; Saminathan et al. 2012). In response to the application of cyclic tensile force to PDL cells, the upregulation of certain osteogenic-specific genes (e.g. bone morphogenetic protein 2 [BMP2], BMP6 and sex-determining region Y-related high mobility group box9 [SOX9]), and downregulation of others (BMP4 and epidermal growth factor [EGF]) was also an important finding (Wescott et al. 2007). Between days one and seven following the commencement of force application, BMPs have been shown to induce expression of runt-related transcription factor 2 (Runx-2) and also bind to osteoblast cell surface receptors, triggering upregulation of osteoblast function (Masella and Meister 2006; Vansant et al. 2018). These findings confirm the complexity of the sequence of events occurring during the week immediately following the initial force application. They also support the proposal that there may be a genetic component to the variation in individual responses to these forces.