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1.
Int J Mol Sci ; 25(11)2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38892016

RESUMO

Transforming growth factor beta (TGF-ß) is ubiquitously found in bone and plays a key role in bone turnover. Mice expressing constitutively active TGF-ß receptor type I (Mx1;TßRICA mice) are osteopenic. Here, we identified the candidate genes involved in bone turnover in Mx1;TßRICA mice using RNA sequencing analysis. A total of 285 genes, including 87 upregulated and 198 downregulated genes, were differentially expressed. According to the KEGG analysis, some genes were involved in osteoclast differentiation (Fcgr4, Lilrb4a), B cell receptor signaling (Cd72, Lilrb4a), and neutrophil extracellular trap formation (Hdac7, Padi4). Lilrb4 is related to osteoclast inhibition protein, whereas Hdac7 is a Runx2 corepressor that regulates osteoblast differentiation. Silencing Lilrb4 increased the number of osteoclasts and osteoclast marker genes. The knocking down of Hdac7 increased alkaline phosphatase activity, mineralization, and osteoblast marker genes. Therefore, our present study may provide an innovative idea for potential therapeutic targets and pathways in TßRI-associated bone loss.


Assuntos
Remodelação Óssea , Osteoclastos , Animais , Camundongos , Remodelação Óssea/genética , Osteoclastos/metabolismo , Osteoclastos/citologia , Osteoblastos/metabolismo , Regulação da Expressão Gênica , Receptor do Fator de Crescimento Transformador beta Tipo I/genética , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Diferenciação Celular/genética , Histona Desacetilases/metabolismo , Histona Desacetilases/genética , Perfilação da Expressão Gênica
2.
Evol Bioinform Online ; 18: 11769343221110656, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35860694

RESUMO

Background: Coding and non-coding short tandem repeats (STRs) facilitate a great diversity of phenotypic traits. The imbalance of mononucleotide A-repeats around transcription start sites (TSSs) was found in 3 mammals: H. sapiens, M. musculus, and R. norvegicus. Principal Findings: We found that the imbalance pattern originated in some vertebrates. A similar pattern was observed in mammals and birds, but not in amphibians and reptiles. We proposed that the enriched A-repeats upstream of TSSs is a novel hallmark of endotherms or warm-blooded animals. Gene ontology analysis indicates that the primary function of upstream A-repeats involves metabolism, cellular transportation, and sensory perception (smell and chemical stimulus) through housekeeping genes. Conclusions: Upstream A-repeats may play a regulatory role in the metabolic process of endothermic animals.

3.
Sci Rep ; 11(1): 18726, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34548536

RESUMO

Patients with systemic lupus erythematosus (SLE) have increased inflammatory cytokines, leading to periodontitis and alveolar bone loss. However, the mechanisms driving this phenomenon are still unknown. Here, we have identified novel therapeutic targets for and mediators of lupus-mediated bone loss using RNA-sequencing (RNA-seq) in a FcγRIIB-/- mouse model of lupus associated osteopenia. A total of 2,710 upregulated and 3,252 downregulated DEGs were identified. The GO and KEGG annotations revealed that osteoclast differentiation, bone mineralization, ossification, and myeloid cell development were downregulated. WikiPathways indicated that Hedgehog, TNFα NF-κB and Notch signaling pathway were also decreased. We identified downregulated targets, Sufu and Serpina12, that have important roles in bone homeostasis. Sufu and Serpina12 were related to Hedgehog signaling proteins, including Gli1, Gli2, Gli3, Ptch1, and Ptch2. Gene knockdown analysis demonstrated that Sufu, and Serpina12 contributed to osteoclastogenesis and osteoblastogenesis, respectively. Osteoclast and osteoblast marker genes were significantly decreased in Sufu-deficient and Serpina12-deficient cells, respectively. Our results suggest that alterations in Hedgehog signaling play an important role in the pathogenesis of osteopenia in FcγRIIB-/- mice. The novel DEGs and pathways identified in this study provide new insight into the underlying mechanisms of mandibular bone loss during lupus development.


Assuntos
Mandíbula/patologia , Osteoporose/genética , Receptores de IgG/genética , Animais , Camundongos , Camundongos Knockout
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