The multiple roles of Thy-1 in cell differentiation and regeneration

Yang, Jie; Zhan, Xiaozhen; Malola, Jonathan; Li, Zhenyan; Pawar, Jogendra Singh; Zhang, Huan-Tian; Zha, Zhengang

doi:10.1016/j.diff.2020.03.003

Cited by 22 publications

(18 citation statements)

References 163 publications

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“…THY1 + subsets, which predominantly localize at the perivascular lesion in the synovium, may be induced due to angiogenesis followed by synovitis and joint damage. In contrast to the differentiation potentials, THY1 interacts with integrin and induces cell apoptosis via activation of the caspase 3/7 pathway [ 28 , 29 ]. Since THY1 expression was enhanced in fibroblasts when joint tissue was injured [ 30 , 31 ], these findings suggest that THY1 exerts to orchestrate the maintenance of joint homeostasis.…”

Section: Discussionmentioning

confidence: 99%

CD34+THY1+ synovial fibroblast subset in arthritic joints has high osteoblastic and chondrogenic potentials in vitro

et al. 2022

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Objective Synovial fibroblasts (SFs) in rheumatoid arthritis (RA) and osteoarthritis (OA) play biphasic roles in joint destruction and regeneration of bone/cartilage as mesenchymal stem cells (MSCs). Although MSCs contribute to joint homeostasis, such function is impaired in arthritic joints. We have identified functionally distinct three SF subsets characterized by the expression of CD34 and THY1 as follows: CD34+THY1+, CD34−THY1−, and CD34−THY1+. The objective of this study was to clarify the differentiation potentials as MSCs in each SF subset since both molecules would be associated with the MSC function. Methods SF subsets were isolated from synovial tissues of 70 patients (RA: 18, OA: 52). Expressions of surface markers associated with MSCs (THY1, CD34, CD73, CD271, CD54, CD44, and CD29) were evaluated in fleshly isolated SF subsets by flow cytometry. The differentiation potentials of osteogenesis, chondrogenesis, and adipogenesis were evaluated with histological staining and a quantitative polymerase chain reaction of differentiation marker genes. Small interfering RNA was examined to deplete THY1 in SFs. Results The expression levels of THY1+, CD73+, and CD271+ were highest and those of CD54+ and CD29+ were lowest in CD34+THY1+ among three subsets. Comparing three subsets, the calcified area, alkaline phosphatase (ALP)-stained area, and cartilage matrix subset were the largest in the CD34+THY1+ subset. Consistently, the expressions of differentiation markers of the osteoblasts (RUNX2, ALPL, and OCN) or chondrocytes (ACAN) were the highest in the CD34+THY1+ subset, indicating that the CD34+THY1+ subset possessed the highest osteogenic and chondrogenic potential among three subsets, while the differentiation potentials to adipocytes were comparable among the subsets regarding lipid droplet formations and the expression of LPL and PPARγ. The knockdown of THY1 in bulk SFs resulted in impaired osteoblast differentiation indicating some functional aspects in this stem-cell marker. Conclusion The CD34+THY1+ SF subset has high osteogenic and chondrogenic potentials. The preferential enhancement of MSC functions in the CD34+THY1+ subset may provide a new treatment strategy for regenerating damaged bone/cartilage in arthritic joints.

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Section: Discussionmentioning

confidence: 99%

CD34+THY1+ synovial fibroblast subset in arthritic joints has high osteoblastic and chondrogenic potentials in vitro

et al. 2022

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“…Remarkably, during initial onset of apoptosis, the surge of caspase-activating proteins is predominantly controlled by the bcl-2 protein family, that are the principal regulator of apoptosis. Bax expression increases, it forms homodimers and activates Caspase-3, the executor of apoptosis, and promotes apoptosis ( Mo et al, 2016 , Yang et al, 2020 ). This infers that at lower concentration treatment leads to senescence and at higher concentration treatment leads to apoptotic induction in a ROS-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Chrysin and Capsaicin induces premature senescence and apoptosis via mitochondrial dysfunction and p53 elevation in Cervical cancer cells

Pawar

Mustafa

Ghosh

2022

Saudi Journal of Biological Sciences

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“…Stem cell fate changes and cytodifferentiation are characterized by a shift in gene expression that involves the coordinated action of transcription factors, DNA methylation and chromatin remodeling activities 96–98 . The cell surface protein Thymocyte Antigen 1 (THY1, also known as CD90) is a marker for MSCs and hDPSCs and plays critical roles in the maintenance of their pluripotency and fate choices 31,99,100 . Our in vitro differentiation assays showed that addition of Nogo-A increases the levels of THY1 in hDPSCs in all experimental setups tested, suggesting that Nogo-A is critical for maintaining the stemness of hDPSCs and inhibiting their differentiation towards osteocytes, adipocytes, and neurons.…”

Section: Discussionmentioning

confidence: 99%

Nogo-A regulates the fate of human dental pulp stem cells towards osteogenic, adipogenic, and neurogenic differentiation

Shen

Lai

Balic

et al. 2022

Preprint

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Human teeth are highly innervated organs that contain a variety of mesenchymal stem cell populations that could be used for cell-based regenerative therapies. Specific molecules are often used in these treatments to favorably modulate stem cells function and fate. Nogo-A, a key regulator of neuronal growth and differentiation, is already used in clinical tissue regeneration trials. While the functions of Nogo-A in neuronal tissues are extensively explored, its role in teeth still remains unknown. In this work, we first immunohistochemically analyzed the distribution of Nogo-A protein in the dental pulp of human teeth. Nogo-A is localized in a variety of cellular and structural components of the dental pulp, including odontoblasts, fibroblasts, neurons and vessels. We also cross-examined Nogo expression in the various pulp cell clusters in a single cell RNA sequencing dataset of human dental pulp, which showed high levels of expression in all cell clusters, including that of stem cells. We then assessed the role of Nogo-A on the fate of human dental pulp stem cells and their differentiation capacity in vitro. Using immunostaining, Alizarin Red S and Oil Red O staining we showed that Nogo-A delayed the differentiation of cultured dental pulp stem cells towards the osteogenic, adipogenic and neurogenic lineages, while addition of the blocking anti-Nogo-A antibody had opposite effects. These results were further confirmed by qRT-PCR, which demonstrated overexpression of genes involved in osteogenic (RUNX2, ALP, SP7/OSX), adipogenic (PPAR-γ2, LPL) and neurogenic (DCX, TUBB3, NEFL) differentiation in presence of the anti-Nogo-A antibody. Conversely, the osteogenic and adipogenic genes were downregulated by Nogo-A. Taken together, our results show that the functions of Nogo-A are not restricted to neuronal cells, but are extended to other cell populations, including dental pulp stem cells. We show that Nogo-A regulates their fates towards osteogenic, adipogenic and neurogenic differentiation, thus indicating its potential use in the clinics.

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The multiple roles of Thy-1 in cell differentiation and regeneration

Cited by 22 publications

References 163 publications

CD34+THY1+ synovial fibroblast subset in arthritic joints has high osteoblastic and chondrogenic potentials in vitro

CD34+THY1+ synovial fibroblast subset in arthritic joints has high osteoblastic and chondrogenic potentials in vitro

Chrysin and Capsaicin induces premature senescence and apoptosis via mitochondrial dysfunction and p53 elevation in Cervical cancer cells

Nogo-A regulates the fate of human dental pulp stem cells towards osteogenic, adipogenic, and neurogenic differentiation

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