How miR-31-5p and miR-33a-5p Regulates SP1/CX43 Expression in Osteoarthritis Disease: Preliminary Insights

被引:14
作者
Costa, Viviana [1 ]
De Fine, Marcello [2 ]
Carina, Valeria [1 ]
Conigliaro, Alice [3 ]
Raimondi, Lavinia [1 ]
De Luca, Angela [1 ]
Bellavia, Daniele [1 ]
Salamanna, Francesca [1 ]
Alessandro, Riccardo [3 ,4 ]
Pignatti, Giovanni [2 ]
Fini, Milena [1 ]
Giavaresi, Gianluca [1 ]
机构
[1] IRCCS Ist Ortoped Rizzoli, SC Sci & Tecnol Chirurg, SS Piattaforma Sci Om Ortopedia Personalizzata, I-40136 Bologna, Italy
[2] IRCCS Ist Ortoped Rizzoli, I-40136 Bologna, Italy
[3] Univ Palermo, Sect Biol & Genet, Dept Biomed Neurosci & Adv Diagnost BiND, I-90133 Palermo, Italy
[4] Ist Ric & Innovaz Biomed IRIB, I-90133 Palermo, Italy
关键词
osteoarthritis; microRNAs; osteoblasts; chondrocytes; SP1; CX43;
D O I
10.3390/ijms22052471
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Osteoarthritis (OA) is a degenerative bone disease that involved micro and macro-environment of joints. To date, there are no radical curative treatments for OA and novel therapies are mandatory. Recent evidence suggests the role of miRNAs in OA progression. In our previous studies, we demonstrated the role of miR-31-5p and miR-33a families in different bone regeneration signaling. Here, we investigated the role of miR-31-5p and miR-33a-5p in OA progression. A different expression of miR-31-5p and miR-33a-5p into osteoblasts and chondrocytes isolated from joint tissues of OA patients classified in based on different Kellgren and Lawrence (KL) grading was highlighted; and through a bioinformatic approach the common miRNAs target Specificity proteins (Sp1) were identified. Sp1 regulates the expression of gap junction protein Connexin43 (Cx43), which in OA drives the modification of (i) osteoblasts and chondrocytes genes expression, (ii) joint inflammation cytokines releases and (iii) cell functions. Concerning this, thanks to gain and loss of function studies, the possible role of Sp1 as a modulator of CX43 expression through miR-31-5p and miR-33a-5p action was also evaluated. Finally, we hypothesize that both miRNAs cooperate to modulate the expression of SP1 in osteoblasts and chondrocytes and interfering, consequently, with CX43 expression, and they might be further investigated as new possible biomarkers for OA.
引用
收藏
页码:1 / 16
页数:15
相关论文
共 39 条
  • [1] MiRNA inhibition in tissue engineering and regenerative medicine
    Beavers, Kelsey R.
    Nelson, Christopher E.
    Duvall, Craig L.
    [J]. ADVANCED DRUG DELIVERY REVIEWS, 2015, 88 : 123 - 137
  • [2] Deregulated miRNAs in bone health: Epigenetic roles in osteoporosis
    Bellavia, D.
    De Luca, A.
    Carina, V
    Costa, V
    Raimondi, L.
    Salamanna, F.
    Alessandro, R.
    Fini, M.
    Giavaresi, G.
    [J]. BONE, 2019, 122 : 52 - 75
  • [3] Cell autonomous requirement of connexin 43 for osteocyte survival: Consequences for endocortical resorption and periosteal bone formation
    Bivi, Nicoletta
    Condon, Keith W.
    Allen, Matthew R.
    Farlow, Nathan
    Passeri, Giovanni
    Brun, Lucas R.
    Rhee, Yumie
    Bellido, Teresita
    Plotkin, Lilian I.
    [J]. JOURNAL OF BONE AND MINERAL RESEARCH, 2012, 27 (02) : 374 - 389
  • [4] Connexin43 and Runx2 Interact to Affect Cortical Bone Geometry, Skeletal Development, and Osteoblast and Osteoclast Function
    Buo, Atum M.
    Tomlinson, Ryan E.
    Eidelman, Eric R.
    Chason, Max
    Stains, Joseph P.
    [J]. JOURNAL OF BONE AND MINERAL RESEARCH, 2017, 32 (08) : 1727 - 1738
  • [5] MiR-33a Controls hMSCS Osteoblast Commitment Modulating the Yap/Taz Expression Through EGFR Signaling Regulation
    Costa, Viviana
    Carina, Valeria
    Raimondi, Lavinia
    De Luca, Angela
    Bellavia, Daniele
    Conigliaro, Alice
    Salamanna, Francesca
    Alessandro, Riccardo
    Fini, Milena
    Giavaresi, Gianluca
    [J]. CELLS, 2019, 8 (12)
  • [6] miR-31-5p Is a LIPUS-Mechanosensitive MicroRNA that Targets HIF-1α Signaling and Cytoskeletal Proteins
    Costa, Viviana
    Carina, Valeria
    Conigliaro, Alice
    Raimondi, Lavinia
    De Luca, Angela
    Bellavia, Daniele
    Salamanna, Francesca
    Setti, Stefania
    Alessandro, Riccardo
    Fini, Milena
    Giavaresi, Gianluca
    [J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2019, 20 (07):
  • [7] Hypoxia-inducible factor 1. may regulate the commitment of mesenchymal stromal cells toward angio-osteogenesis by mirna-675-5P
    Costa, Viviana
    Raimondi, Lavinia
    Conigliaro, Alice
    Salamanna, Francesca
    Carina, Valeria
    De Luca, Angela
    Bellavia, Daniele
    Alessandro, Riccardo
    Fini, Milena
    Giavaresi, Gianluca
    [J]. CYTOTHERAPY, 2017, 19 (12) : 1412 - 1425
  • [8] MiR-675-5p supports hypoxia induced epithelial to mesenchymal transition in colon cancer cells
    Costa, Viviana
    Lo Dico, Alessia
    Rizzo, Aroldo
    Rajata, Francesca
    Tripodi, Marco
    Alessandro, Riccardo
    Conigliaro, Alice
    [J]. ONCOTARGET, 2017, 8 (15) : 24292 - 24302
  • [9] Sp1/Sp3 and PU.1 differentially regulate β5 integrin gene expression in macrophages and osteoblasts
    Feng, X
    Teitelbaum, SL
    Quiroz, ME
    Cheng, SL
    Lai, CF
    Avioli, LV
    Ross, FP
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (12) : 8331 - 8340
  • [10] Proteomic Analysis of Connexin 43 Reveals Novel Interactors Related to Osteoarthritis
    Gago-Fuentes, Raquel
    Fernandez-Puente, Patricia
    Megias, Diego
    Carpintero-Fernandez, Paula
    Mateos, Jesus
    Acea, Benigno
    Fonseca, Eduardo
    Javier Blanco, Francisco
    Dolores Mayan, Maria
    [J]. MOLECULAR & CELLULAR PROTEOMICS, 2015, 14 (07) : 1831 - 1845