TGF-β1 is Involved in Vitamin D-Induced Chondrogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells by Regulating the ERK/JNK Pathway

Abstract

Background/Aims: Osteoarthritis (OA) is characterized by degradation of cartilage, sole cell type of which is chondrocytes. Bone marrow-derived mesenchymal stem cells (BMSCs) possess multipotency and can be directionally differentiated into chondrocytes under stimulation. This study was aimed to explore the possible roles of vitamin D and transforming growth factor-β1 (TGF-β1) in the chondrogenic differentiation of BMSCs. Methods: BMSCs were isolated from femurs and tibias of rats and characterized by flow cytometry. After stimulation with vitamin D, BMSC proliferation and migration were measured by Cell Counting Kit-8 (CCK-8) and Transwell assays, respectively. Chondrogenic differentiation was estimated through expression levels of specific markers by qRT-PCR and Western blot analysis. After stable transfection, the effects of aberrantly expressed TGF-β1 on vitamin D-induced alterations, including BMSC viability, migration and chondrogenic differentiation, were all evaluated utilizing CCK-8 assay, Transwell assay, qRT-PCR and Western blot analysis. Finally, the phosphorylation levels of key kinases in the extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) pathways were determined by Western blot analysis. Results: Vitamin D remarkably promoted BMSC viability, migration and chondrogenic differentiation. These alterations of BMSCs induced by vitamin D were reinforced by TGF-β1 overexpression while were reversed by TGF-β1 silencing. Additionally, the phosphorylation levels of ERK, JNK and c-Jun were enhanced by TGF-β1 overexpression but were reduced by TGF-β1 knockdown. Conclusion: Vitamin D promoted BMSC proliferation, migration and chondrogenic differentiation. TGF-β1 might be implicated in the vitamin D-induced alterations of BMSCs through regulating ERK/JNK pathway.

The Influence of Hyperosmolarity in the Intervertebral Disc on the Proliferation and Chondrogenic Differentiation of Nucleus Pulposus-Derived Mesenchymal Stem Cells

“…However, it has already been outlined from several stem cell systems that the ERK pathway is involved in chondrogenic differentiation [Jiang et al, 2017;Wang et al, 2017a;Wu et al, 2018], and plays a vital role in the proliferation of MSCs [Kim et al, 2015;Yang et al, 2017]. Therefore, we investigated the effect of hyperosmolarity on the activation of the ERK pathway, and the regulatory role of this pathway on the proliferation and chondrogenic differentiation of NP-MSCs under the hyperosomotic conditions of IVD.…”

“…However, there is a paucity of data about the influence of hyperosmolarity of IVD on the proliferation and chondrogenic differentiation of NP-MSCs. The extracellular signal-regulated kinase (ERK) pathway is a mitogen-activated protein kinase (MAPK) pathway, which is involved in the chondrogenic differentiation [Jiang et al, 2017;Wang et al, 2017a;Wu et al, 2018] and proliferation [Kim et al, 2015;Yang et al, 2017] of MSCs. To the best of our knowledge, no literature is available that describes the regulatory role of ERK in the proliferation and chondrogenic differentiation of NP-MSCs under the hyperosmotic condition of IVD.…”

The positive effect of chick embryo and nutrient mixture on bone marrow- derived mesenchymal stem cells from aging rats

“…Jiang et al . indicated that Vitamin D remarkably promoted BMSC viability, migration and chondrogenic differentiation 32 . In this work, we developed an aging rat model induced by D-gal, which was now recognized as an inducer of aging reagents that was accelerated senescence in rats 33 .…”

Chondrogenic differentiation of bone marrow-derived mesenchymal stem cells following transfection with Indian hedgehog and sonic hedgehog using a rotary cell culture system

“…Joint articular cartilage degeneration plays a fundamental role in the pathogenesis of osteoarthritis (OA), which is characterized by joint pain, stiffness, and limited mobility [2]. Bone marrow-derived mesenchymal stem cells (BMSCs) have been widely used in tissue regeneration due to their potential to differentiate into multiple cell lineages including osteocytes, adipocytes, and chondrocytes [3, 4]. However, BMSC-based cartilage tissue regeneration biochemically and biomechanically adequate for clinical use has not been successful and is hindered by chondrogenic induction and hypertrophy.…”