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Physiological aspects of blastema formation in mice
Published in David M. Gardiner, Regenerative Engineering and Developmental Biology, 2017
It is relevant to note that when digit regeneration is induced by treatment with BMP2, the induced response forms new bone by establishing a novel endochondral ossification center at the wound site, and this center organizes the formation of newly regenerated bone (Yu et al. 2010, 2012). Thus, the differentiation phase of endogenous regeneration does not involve a re-development response, despite the fact that stump cells retain the capacity to affect a re-development response. This observation suggests that this phase of the regenerative response evolved a completely novel mechanism for bone formation that may reflect inherent limitations imposed by the availability of progenitor cells in the stump wound. For example, a re-development response would require the availability of chondrogenic progenitor cells to form an endochondral ossification center, but only osteogenic progenitor cells appear to be available at the amputation wound. The BMP2-induced regenerative response involves the secondary activation of an SDF1/CXCR4-mediated migration response that functions in the recruitment of progenitor cells, and SDF1 is not expressed at the non-regenerative amputation wound (Lee et al. 2013). The SDF1/CXCR4 signaling is functional in the endogenous regenerative response, so it makes sense that only osteogenic progenitor cells are responsive to this recruitment signal.
Association between Bone Morphogenetic Protein 2 Gene Polymorphisms and Skeletal Fluorosis of The Brick-tea Type Fluorosis in Tibetans and Kazakhs, China
Published in International Journal of Environmental Health Research, 2021
Qun Lou, Ning Guo, Wei Huang, Liaowei Wu, Mengyao Su, Yang Liu, Xiaona Liu, Bingyun Li, Yanmei Yang, Yanhui Gao
SF is a chronic metabolic bone disease, characterized by acceleration of bone turnover with active osteoblastic activity. Thus, some signaling molecules related to osteoblastic activity are reported to be involved in the pathogenesis of skeletal fluorosis(Everett 2010). BMP2, a critical regulator in bone tissue formation, plays an important role in inducing osteogenesis and stimulating the proliferation of osteoclasts. In vitro studies have reported sodium fluoride could promote BMP2 expression to induce proliferation of human osteosarcoma MG-63 cells, a human osteoblast-like cell lines (Wei et al. 2014). In the rat model of fluorosis established by NaF stimulation, the expression of BMP2 is up-regulated in osteoblast cells (Zhang et al. 2006). Therefore, BMP2 might play an important role in the pathogenesis of skeletal fluorosis. There are many pieces of evidence indicate that some SNPs of BMP2, such as Rs1980499, Rs235739, Rs235764 and Rs996544, are predominantly associated with osteoblast differentiation and influence bone mineral density (BMD) (Reneland et al. 2005; Tranah et al. 2008; Deng et al. 2013). However, the relationship between these SNPs and skeletal fluorosis is unclear.
The improvement of calvarial bone healing by durable nanogel-crosslinked materials
Published in Journal of Biomaterials Science, Polymer Edition, 2018
Pornkawee Charoenlarp, Arun Kumar Rajendran, Rie Fujihara, Taisei Kojima, Ken-ichi Nakahama, Yoshihiro Sasaki, Kazunari Akiyoshi, Masaki Takechi, Sachiko Iseki
Growth factors (GFs) are biologically active polypeptides that have also been used to improve scaffold bioactivity as a result of their ability to stimulate stem and precursor cell maintenance, proliferation, and differentiation towards specific lineages. BMP2 belongs to transforming growth factor-β (TGF-β) superfamily is considered as a potent osteoinductive growth factor for osteogenic differentiation of various stem cells. Therefore, BMP2 has been widely used for bone regeneration applications [12,13]. FGF18 is a member of the FGF family and the candidate growth factor for bone regeneration since it is involved in osteogenesis during skeletal development [14,15]. Several studies have shown that FGF18 can promote differentiation of osteoblastic cells in fetal skull bone formation by upregulating BMP2 expression, accompanied by Noggin downregulation [16,17]. However, FGF18 itself cannot accelerates bone formation in mouse calvarial bone defect model [18]. Combination of hFGF18 and hBMP2 showed enhanced and stable bone regeneration in mouse calvarial bone healing, so FGF18 activated bone regeneration only in the presence of BMP2 [18]. Therefore, co-administration of these two GFs with appropriate scaffold would be a promising strategy for bone regenerative therapy.
PEI-modified diatomite/chitosan composites as bone tissue engineering scaffold for sustained release of BMP-2
Published in Journal of Biomaterials Science, Polymer Edition, 2021
Xiangyu Wang, Yufang Li, Wenjuan Ren, Ruxia Hou, Haifeng Liu, Ran Li, Shouji Du, Lu Wang, Junyu Liu
Diatomite, also known as diatomaceous earth (DE), is an inexpensive fossil compound formed by the fragments of diatom siliceous skeletons at the bottom of lakes or oceans over millions of years. It has similar physicochemical properties as the fabricated silica nanoparticles [8, 9]. The DE micro shells, characterized by unique pill-box microstructures, possess porosity in the micro/nanoscale range, high surface area, superior biocompatibility and surface hydroxyl groups. Thus, these shells represent a promising, abundant and low-cost biomaterial for drug delivery applications [10, 11]. On the other hand, the drug delivery capacity in the target area, which can result in a high local concentration with few side effects, is an important evaluation index for the local delivery systems. Bone morphogenetic protein-2 (BMP-2), which has been approved by the US Food and Drug Administration (FDA) for several orthopedic diseases since 2002 [12], is a growth factor with an obvious osteogenic effect. However, the clinical results involving BMP-2 are not always ideal. For instance, the osteogenic effect of low dose BMP-2 is not optimal [13]. Besides, the allergic dosage can cause a series of side effects [14–16]. Therefore, controlling the dose of BMP-2 and improving its curative effect are of high importance. In fact, in some cases, the protein is incorporated in the material by incubation, and the initial burst release appears subsequently, unless the material–protein interaction occurs [17]. Therefore, an appropriate protein adsorption method is required to obtain an enhanced drug load capacity and slow protein release. Currently, the common methods to improve the protein adsorption are based on enhancing the specific surface area [18] and surface functionalization approach [19, 20]. The bare DE surface exhibits highly negative charges due to the presence of hydroxyl groups (–OH), thus, promoting the cationic adsorption. However, the scaffolds with negative surface charges are not conducive for the adhesion of BMP-2 due to the net negative charge of BMP-2 [21]. Thus, it is important to modify the DE surface with positively charged surfactants or chemical moieties. As a cationic polyelectrolyte, polyethyleneimine (PEI) has been widely used for the modification of biochars, nanoparticles, extracellular vesicles, liposomes, etc., so as to improve their delivery efficiency [22–25]. PEI molecules of lower molecular weight are also efficient reagents with much lower cytotoxicity [26]. After treatment with PEI, the surface charge of the modified diatomite (MDE) turns positive, and the BMP-2 molecules can be effectively adsorbed on the diatomite surface through electrostatic attraction. Furthermore, many literature studies have reported that the surface potential of scaffold affects the cell morphology and density during cell adhesion and proliferation [27, 28]. As a consequence, the modification of DE by PEI is beneficial not only for protein adsorption, but also for improving the biocompatibility of the material.