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The Spontaneous Induction of Bone Formation by Intrinsically Osteoinductive Bioreactors for Human Patients
Published in Ugo Ripamonti, The Geometric Induction of Bone Formation, 2020
The paper of Lismaa et al. (2018) reports comparative regenerative mechanisms across animal phylogeny and taxa, “showing wide variations in regenerative competence” (Lismaa et al. 2018). The paper of De Robertis, “Evo-Devo: Variations on ancestral themes”, shows “that conserved gene networks already present in the archetypal ancestor were modified to generate the wonderful diversity of animal life on Earth today”, and that the Hox genes are conserved between Drosophila and vertebrates (De Robertis 2008). There are thus phylogenetically ancient pathways between animal phyla with high degrees of conservation, including genes responsible for tissue regeneration (De Robertis 2008; Lismaa et al. 2018). Results obtained in non-human primate species may only indicate that similar repair mechanisms may operate in Homo sapiens, though translation in clinical contexts is altogether rather speculative (Ferretti et al. 2010; Ripamonti et al. 2014).
Disorders of Growth and Differentiation
Published in Jeremy R. Jass, Understanding Pathology, 2020
Cell function is divided into three broad categories: (1) proliferation, (2) death, and (3) differentiation. Cell proliferation focuses on the cell cycle (mitogenesis) and the mechanisms that initiate and control this process. Cell death implies the programmed demise of individual cells known as apoptosis. The balance of cell generation and cell death will determine whether an organ grows, shrinks or remains the same size. Differentiation is concerned with the control of gene induction which will provide a cell with its repertoire of housekeeping requirements as well as its specialised functions. Although proliferation, death and differentiation must be studied in isolation, because each is extraordinarily complex, they are integrated not only at the level of the cell but also at the level of tissues. The global orchestration of proliferation, death and differentiation is encountered in its most dynamic and extraordinary form during embryological development. However the Hox genes, which are restricted to the animal kingdom and occur in clustered arrays for sequential activation of target genes during embryological development, also function in the stem cells of adult tissues. This is one of many examples of a single gene having multiple functions. The following account of the proliferation, death and differentiation of cells will include issues that are of particular interest to the anatomical pathologist because of their practical importance in tissue diagnosis.
Retinoic acid signaling in spermatogenesis and male (in)fertility
Published in Rajender Singh, Molecular Signaling in Spermatogenesis and Male Infertility, 2019
Dario Santos, Rita Payan-Carreira
Over 500 genes have been put forth as being regulatory targets of RA. In some cases, direct regulation was demonstrated driven by ligand RAR/RXR heterodimers bound to RAREs (43). RA induces the transcription of many genes encoding proteins that are involved in cell differentiation and a variety of biochemical processes (19,44). The first RAR target genes to be discovered were RARβ, laminin B1, CRBP and CRABP (29). Moreover, proteins involved in RA metabolism, such as CYP26, are also directly regulated by RA (43). The Hox gene, one of the most well-known target genes of RARs, is a key regulator of pattern formation in vertebrates during development (45). RARs also regulate factors involved in metabolism (29).
MicroRNA-582-3p regulates osteoporosis through regulating homeobox A10 and osteoblast differentiation
Published in Immunopharmacology and Immunotoxicology, 2022
Jian Yin, Wei Xiao, Qingbin Zhao, Jungang Sun, Wenzheng Zhou, Wei Zhao
HOX genes are expressed in almost all eukaryotic cells. The HOX gene is a class of evolutionarily highly conserved genes and a dominant gene for vertebrate growth and cell differentiation [40]. It can participate in body development, cell identification, differentiation, metabolism, apoptosis, autophagy and plays roles in tumorigenesis and progression [41]. HOXA10, a bone morphogenetic protein (BMP) 2 inducible gene, contributes to osteogenic lineage determination by activating the osteogenic transcription factor Runx2 and modulating the expression of osteoblast genes [42]. Numerous studies have shown that HOXA10 is also involved in bone formation and healing in adults [43]. HOXA10 is significantly up-regulated in the early stages of BMP2-induced osteogenic differentiation, and it is mainly expressed in differentiated cells and mature chondrocytes in the mid-axial bone and limb bone growth regions [44].
Homeobox A5 and A9 expression and beta-thalassemia
Published in British Journal of Biomedical Science, 2021
EAE Badr, IE-T El-Sayed, MKR Alasadi
Data from zebrafish point to Homeobox (Hox) genes having an important role in normal haematopoiesis related to haematopoietic stem cells (HSCs) and early haematopoietic progenitors [6]. The Hox genes contain several clusters (A-D). Each cluster consists of paralog groups with nine to eleven members assigned on the basis of sequence similarity and relative position within the cluster [7]. The HOXA family encodes proteins that contain the DNA-binding homeobox motif and controls the early patterns of embryo segmentation. Although HOX expression is typically inhibited in adults, reactivation may occur with various homoeostatic cellular processes including haematopoiesis. Hox genes are required for the maintenance of progenitor or stem cell status, promoting their proliferation. HoxA9 is the most preferentially expressed Hox gene in human CD34+ HSCs and early haematopoietic progenitors [8]. HoxA5 has two effects on erythropoiesis: it causes a predominance of mature erythroid lineage cells and the partial apoptosis of erythroid progenitors. RNA-seq indicates that multiple biological processes including erythrocyte homoeostasis, cell metabolism, and apoptosis are modified by HoxA5 [9]. We hypothesized roles for HoxA9 and HoxA5 in β-thalassemia.
A Novel lncRNA HOXC-AS3 Acts as a miR-3922-5p Sponge to Promote Breast Cancer Metastasis
Published in Cancer Investigation, 2020
Sheng-Hong Shi, Jing Jiang, Wei Zhang, Long Sun, Xu-Jun Li, Chao Li, Qi-Dong Ge, Zhi-Gang Zhuang
HOXC-AS3 located at chromosome 12q13.13 was an antisense transcript of HOXC10. HOX genes are essential for morphogenesis, development, and tumorigenesis (34). The dysregulation of HOXC-AS3 gene has been reported in various cancers (19,35,36). In addition, previous studies have reported that lncRNA may function as competing endogenous RNA to sponge miRNA, thereby modulating the derepression of miRNA targets and imposing an additional level of post-transcriptional regulation (37,38). In the present study, miR-3922-5p was predicted to contain a binding site for HOXC-AS3 by bioinformatics analysis. We found that inhibition of HOXC-AS3 repressed breast cancer cells invasion and migration both in vitro and in vivo. HOXC-AS3 could bind to and regulate the expression of miR-3922-5p, and showed a negative correlation with miR-3922-5p in lung metastatic breast cancer. These results indicate that HOXC-AS3 may participate in the tumorigenesis of breast cancer by serving as a sponge for miR-3922-5p.