biostudies-literatureClayton SWNational Institutes of HealthNIAMS NIH HHSNIH HHS21364https://www.ebi.ac.uk/biostudies/studies/S-EPMC7721728biostudies-literatureUnknown10(1)Previously, we showed that embryonic deletion of TGF-β type 2 receptor in mouse sclerotome resulted in defects in fibrous connective tissues in the spine. Here we investigated how TGF-β regulates expression of fibrous markers: Scleraxis, Fibromodulin and Adamtsl2. We showed that TGF-β stimulated expression of Scleraxis mRNA by 2 h and Fibromodulin and Adamtsl2 mRNAs by 8 h of treatment. Regulation of Scleraxis by TGF-β did not require new protein synthesis; however, protein synthesis was required for expression of Fibromodulin and Adamtsl2 indicating the necessity of an intermediate. We subsequently showed Scleraxis was a potential intermediate for TGF-β-regulated expression of Fibromodulin and Adamtsl2. The canonical effector Smad3 was not necessary for TGF-β-mediated regulation of ScleraScientific reportsCanonical and noncanonical TGF-β signaling regulate fibrous tissue differentiation in the axial skeleton.PMC7721728R56 AR053860T32 AR069516R01 AR053860Ban GILiu CSerra RClayton SWfalseCanonical and noncanonical TGF-β signaling regulate fibrous tissue differentiation in the axial skeleton.Previously, we showed that embryonic deletion of TGF-β type 2 receptor in mouse sclerotome resulted in defects in fibrous connective tissues in the spine. Here we investigated how TGF-β regulates expression of fibrous markers: Scleraxis, Fibromodulin and Adamtsl2. We showed that TGF-β stimulated expression of Scleraxis mRNA by 2 h and Fibromodulin and Adamtsl2 mRNAs by 8 h of treatment. Regulation of Scleraxis by TGF-β did not require new protein synthesis; however, protein synthesis was required for expression of Fibromodulin and Adamtsl2 indicating the necessity of an intermediate. We subsequently showed Scleraxis was a potential intermediate for TGF-β-regulated expression of Fibromodulin and Adamtsl2. The canonical effector Smad3 was not necessary for TGF-β-mediated regulation of Sclera2020-01-01T00:00:00Z2020 Dec2025-04-19T06:54:51.841Z2025-04-19T06:54:51.841ZS-EPMC77217283328879510.1038/s41598-020-78206-4