Expression of TGF-β Signaling Regulator RBPMS (RNA-Binding Protein With Multiple Splicing) Is Regulated by IL-1β and TGF-β Superfamily Members, and Decreased in Aged and Osteoarthritic Cartilage

Abstract

Objective. RNA-binding protein with multiple splicing (RBPMS) has been shown to physically interact with Smads and enhance transforming growth factor-β (TGF-β)-mediated Smad2/3 transcriptional activity in mammalian cells. Objective of this study was to examine whether expression of RBPMS is regulated by interleukin-1β (IL)-1β and TGF-β superfamily growth factors and whether expression of RBPMS is altered during aging and experimental osteoarthritis. Methods. Expression of RBPMS protein was investigated in chondrocyte cell lines of murine (H4) and human (G6) origin using Western blot analysis. Regulation of RBPMS expression in H4 chondrocytes at mRNA level was done by reverse transcriptase-quantitative polymerase chain reaction. Furthermore, characterization of Smad signaling pathways regulating RBPMS expression was performed by blocking studies using small molecule inhibitors or by transfection studies with adenoviral vector constructs (constitutive-active ALK1 and constitutive-active ALK5). Expression of RBPMS in cartilage of different age groups of C57BL/6N mice (6 months and 20 months) and in a surgically induced osteoarthritis (OA) mouse model was analyzed using immunohistochemistry. Results. RBPMS was shown to be expressed in chondrocytes and cartilage of murine, human, and bovine origin. TGF-β inhibited RBPMS expression while BMP2 and IL-1β increased its expression. TGF-β-induced inhibition was blocked by ALK5 inhibitor. Overexpression of ca-ALK1 stimulated RBPMS expression. Moreover, RBPMS expression was found to be reduced with ageing and in OA pathogenesis. Conclusions. Expression of RBPMS in chondrocytes is regulated by TGF-β superfamily members and IL-1β, indicating a counter-regulatory mechanism. Expression of RBPMS, in cartilage and its reduction during ageing and OA might suggest its potential role in the maintenance of normal articular cartilage.

Aberrant activation of latent transforming growth factor-β initiates the onset of temporomandibular joint osteoarthritis

“…The TGF-I was used to inhibit TGF-β1 signalling to rescue cartilage damage induced by OA. 56 Moreover, the TGF-I ameliorated the abnormal role of high levels of active TGF-β1 in bone formation and directly attenuated Smad2/3 phosphorylation. 57 , 58 In our study, injection of the TGF-I significantly decreased the number of p-Smad2/3-positive cells in the condylar cartilage and subchondral bone in the TMD model.…”

Epigenetic analysis of Paget’s disease of bone identifies differentially methylated loci that predict disease status

“…Additionally, six Bonferroni significant DMR in gene bodies were identified. These were located within genes with functions related to mitosis and ciliogenesis (SDCCAG8) ( Insolera et al, 2014 ): TGFB1-mediated signaling (RBPMS) ( Shanmugaapriya et al, 2016 ); calcium signaling (CACNA1B) ( Blair et al, 2007 ); protein ubiquitination (HSPA13) ( Kaye et al, 2000 ); cytoskeletal organization (PARD3B) ( Kohjima et al, 2002 ); and histone acetylation (BRD1) ( Mishima et al, 2014 ).…”

Divalent Metal Transporter 1 Knock-Down Modulates IL-1β Mediated Pancreatic Beta-Cell Pro-Apoptotic Signaling Pathways through the Autophagic Machinery

“…Further, IL1F9 has been suggested to activate NF-κB, MAPKs, and JNK, resulting in enhanced inflammatory responses [ 87 ]. In addition, the RNA-binding protein with multiple splicing (RBPMS), previously uncharacterized in pancreatic β-cells, is known to be up-regulated by pro-inflammatory cytokines like TGF-β and IL-1β [ 88 , 89 ]. Two previous GWAS meta-analyses identified T2D-associated polymorphism (rs9282541 and rs1800977) of a gene encoding a unique ABCA1 [ 90 , 91 ], involved in insulin secretion, glucose tolerance, and cholesterol homeostasis [ 92 , 93 , 94 , 95 ].…”