scholarly journals Cyclooxygenase 2 augments osteoblastic but suppresses chondrocytic differentiation of CD90+ skeletal stem cells in fracture sites

2019 ◽  
Vol 5 (7) ◽  
pp. eaaw2108 ◽  
Author(s):  
Samiksha Wasnik ◽  
Ram Lakhan ◽  
David J. Baylink ◽  
Charles H. Rundle ◽  
Yi Xu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Tissue Repair ◽  
Bone Repair ◽  
Cyclooxygenase 2 ◽  
Fracture Repair ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Cox 2 ◽  
Chondrocytic Differentiation ◽  
Canonical Wnt

Cyclooxygenase 2 (COX-2) is essential for normal tissue repair. Although COX-2 is known to enhance the differentiation of mesenchymal stem cells (MSCs), how COX-2 regulates MSC differentiation into different tissue-specific progenitors to promote tissue repair remains unknown. Because it has been shown that COX-2 is critical for normal bone repair and local COX-2 overexpression in fracture sites accelerates fracture repair, this study aimed to determine the MSC subsets that are targeted by COX-2. We showed that CD90+ mouse skeletal stem cells (mSSCs; i.e., CD45−Tie2−AlphaV+ MSCs) were selectively recruited by macrophage/monocyte chemoattractant protein 1 into fracture sites following local COX-2 overexpression. In addition, local COX-2 overexpression augmented osteoblast differentiation and suppressed chondrocyte differentiation in CD90+ mSSCs, which depended on canonical WNT signaling. CD90 depletion data demonstrated that local COX-2 overexpression targeted CD90+ mSSCs to accelerate fracture repair. In conclusion, CD90+ mSSCs are promising targets for the acceleration of bone repair.

scholarly journals Monocyte Chemoattractant Protein 1–Mediated Migration of Mesenchymal Stem Cells Is a Source of Intimal Hyperplasia

2013 ◽  
Vol 33 (6) ◽  
pp. 1271-1279 ◽  
Author(s):  
Monika K. Grudzinska ◽  
Ewa Kurzejamska ◽  
Krzysztof Bojakowski ◽  
Joanna Soin ◽  
Michael H. Lehmann ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Intimal Hyperplasia ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein

scholarly journals Monocyte Chemoattractant Protein-1 stimulates the differentiation of rat stem and progenitor Leydig cells during regeneration

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiangcheng Zhan ◽  
Jingwei Zhang ◽  
Saiyang Li ◽  
Xiaolu Zhang ◽  
Linchao Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Serum Testosterone ◽  
Monocyte Chemoattractant Protein 1 ◽  
Rat Testis ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein

Abstract Background Monocyte chemoattractant protein-1(MCP-1) is a chemokine secreted by Leydig cells and peritubular myoid cells in the rat testis. Its role in regulating the development of Leydig cells via autocrine and paracrine is still unclear. The objective of the current study was to investigate the effects of MCP-1 on Leydig cell regeneration from stem cells in vivo and on Leydig cell development in vitro. Results Intratesticular injection of MCP-1(10 ng/testis) into Leydig cell-depleted rat testis from post-EDS day 14 to 28 significantly increased serum testosterone and luteinizing hormone levels, up-regulated the expression of Leydig cell proteins, LHCGR, SCARB1, CYP11A1, HSD3B1, CYP17A1, and HSD17B3 without affecting progenitor Leydig cell proliferation, as well as increased ERK1/2 phosphorylation. MCP-1 (100 ng/ml) significantly increased medium testosterone levels and up-regulated LHCGR, CYP11A1, and HSD3B1 expression without affecting EdU incorporation into stem cells after in vitro culture for 7 days. RS102895, a CCR2 inhibitor, reversed MCP-1-mediated increase of testosterone level after culture in combination with MCP-1. Conclusion MCP-1 stimulates the differentiation of stem and progenitor Leydig cells without affecting their proliferation.

scholarly journals Immunomodulatory Effects of MSCs in Bone Healing

2019 ◽  
Vol 20 (21) ◽  
pp. 5467 ◽  
Author(s):  
Dalia Medhat ◽  
Clara I. Rodríguez ◽  
Arantza Infante
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune System ◽  
Bone Repair ◽  
Human Mesenchymal Stem Cells ◽  
Cell Types ◽  
Bone Diseases ◽  
Fracture Repair ◽  
Innate Immune ◽  
A Cell

Mesenchymal stem cells (MSCs) are capable of differentiating into multilineage cells, thus making them a significant prospect as a cell source for regenerative therapy; however, the differentiation capacity of MSCs into osteoblasts seems to not be the main mechanism responsible for the benefits associated with human mesenchymal stem cells hMSCs when used in cell therapy approaches. The process of bone fracture restoration starts with an instant inflammatory reaction, as the innate immune system responds with cytokines that enhance and activate many cell types, including MSCs, at the site of the injury. In this review, we address the influence of MSCs on the immune system in fracture repair and osteogenesis. This paradigm offers a means of distinguishing target bone diseases to be treated with MSC therapy to enhance bone repair by targeting the crosstalk between MSCs and the immune system.

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