scholarly journals Hypoxia Activates the PTHrP –MEF2C Pathway to Attenuate Hypertrophy in Mesenchymal Stem Cell Derived Cartilage

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
David C. Browe ◽  
Cynthia M. Coleman ◽  
Frank P. Barry ◽  
Stephen J. Elliman
Keyword(s):  
Oxygen Tension ◽  
Mechanism Of Action ◽  
Low Oxygen ◽  
Repair Capacity ◽  
Beneficial Effects ◽  
Chondrogenic Potential ◽  
Low Oxygen Tension ◽  
Cellular Source

Abstract Articular cartilage lacks an intrinsic repair capacity and due to the ability of mesenchymal stem cells (MSCs) to differentiate into chondrocytes, MSCs have been touted as a cellular source to regenerate damaged cartilage. However, a number of prevailing concerns for such a treatment remain. Generally, administration of MSCs into a cartilage defect results in poor regeneration of the damaged cartilage with the repaired cartilage consisting primarily of fibro-cartilage rather than hyaline cartilage. Methods that improve the chondrogenic potential of transplanted MSCs in vivo may be advantageous. In addition, the proclivity of MSC-derived cartilage to undergo hypertrophic differentiation or form bone in vivo also remains a clinical concern. If MSC-derived cartilage was to undergo hypertrophic differentiation in vivo, this would be deleterious in a clinical setting. This study focuses on establishing a mechanism of action by which hypoxia or low oxygen tension can be used to both enhance chondrogenesis and attenuate hypertrophic differentiation of both MSC and ATDC5 derived chondrocytes. Having elucidated a novel mechanism of action, the subsequent goals of this study were to develop an in vitro culture regime to mimic the beneficial effects of physiological low oxygen tension in a normoxic environment.

Embryo culture at a reduced oxygen concentration of 5%: a mini review

Zygote ◽  
2019 ◽  
Vol 27 (6) ◽  
pp. 355-361 ◽  
Author(s):  
R. Sciorio ◽  
G.D. Smith
Keyword(s):  
Oxygen Tension ◽  
Embryo Development ◽  
Atmospheric Oxygen ◽  
Embryo Implantation ◽  
Critical Role ◽  
Low Oxygen ◽  
Physiological Level ◽  
Low Oxygen Tension

SummaryThe optimum oxygen tension for culturing mammalian embryos has been widely debated by the scientific community. While several laboratories have moved to using 5% as the value for oxygen tension, the majority of modern in vitro fertilization (IVF) laboratory programmes still use 20%. Several in vivo studies have shown the oxygen tension measured in the oviduct of mammals fluctuates between 2% and 8% and in cows and primates this values drops to <2% in the uterine milieu. In human IVF, a non-physiological level of 20% oxygen has been used in the past. However, several studies have shown that atmospheric oxygen introduces adverse effects to embryo development, not limited to numerous molecular and cellular physiology events. In addition, low oxygen tension plays a critical role in reducing the high level of detrimental reactive oxygen species within cells, influences embryonic gene expression, helps with embryo metabolism of glucose, and enhances embryo development to the blastocyst stage. Collectively, this improves embryo implantation potential. However, clinical studies have yielded contradictory results. In almost all reports, some level of improvement has been identified in embryo development or implantation, without any observed drawbacks. This review article will examine the recent literature and discusses ongoing efforts to understand the benefits that low oxygen tension can bring to mammal embryo development in vitro.

scholarly journals Comparative Genomics Shows Differences in the Electron Transport and Carbon Metabolic Pathways of Mycobacterium africanum relative to Mycobacterium tuberculosis and suggests an adaptation to low oxygen tension

2019 ◽  
Author(s):  
Boatema Ofori-Anyinam ◽  
Abi Janet Riley ◽  
Tijan Jobarteh ◽  
Ensa Gitteh ◽  
Binta Sarr ◽  
...  
Keyword(s):  
Electron Transport ◽  
Oxygen Tension ◽  
Significant Proportion ◽  
Sensu Stricto ◽  
Low Oxygen ◽  
Low Oxygen Tension ◽  
Genes Encoding ◽  
Mycobacterium Africanum

SummaryThe geographically restricted Mycobacterium africanum lineages (MAF) are primarily found in West Africa, where they account for a significant proportion of tuberculosis. Despite this phenomenon, little is known about the co-evolution of these ancient lineages with West Africans. MAF and M. tuberculosis sensu stricto lineages (MTB) differ in their clinical, in vitro and in vivo characteristics for reasons not fully understood. Therefore, we compared genomes of 289 MAF and 205 MTB clinical isolates from the 6 main human-adapted M. tuberculosis complex lineages, for mutations in their Electron Transport Chain and Central Carbon Metabolic pathway in order to explain these metabolic differences. Furthermore, we determined, in silico, whether each mutation could affect the function of genes encoding enzymes in these pathways.We found more mutations with the potential to affect enzymes in these pathways in MAF lineages compared to MTB lineages. We also found that similar mutations occurred in these pathways between MAF and some MTB lineages.Generally, our findings show further differences between MAF and MTB lineages that may have contributed to the MAF clinical and growth phenotype and indicate potential adaptation of MAF lineages to a distinct ecological niche, which we suggest includes areas characterized by low oxygen tension.

Effects of in vitro low oxygen tension preconditioning of buccal fat pad stem cells on in Vivo articular cartilage tissue repair

Life Sciences ◽  
2021 ◽  
pp. 119728
Author(s):  
Fatemeh Dehghani Nazhvani ◽  
Leila Mohammadi Amirabad ◽  
Arezo Azari ◽  
Hamid Namazi ◽  
Simzar Hosseinzadeh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Articular Cartilage ◽  
Tissue Repair ◽  
Cartilage Tissue ◽  
Low Oxygen ◽  
Fat Pad ◽  
Buccal Fat Pad ◽  
Low Oxygen Tension

scholarly journals In vivo analysis of DNA-protein interactions on the human erythropoietin enhancer.

1997 ◽  
Vol 17 (2) ◽  
pp. 851-856 ◽  
Author(s):  
B Hu ◽  
E Wright ◽  
L Campbell ◽  
K L Blanchard
Keyword(s):  
Oxygen Tension ◽  
Protein Interactions ◽  
Proximal Promoter ◽  
Low Oxygen ◽  
Initiation Rate ◽  
Cobalt Exposure ◽  
In Cells ◽  
Dna Protein Interactions

The erythropoietin (EPO) gene is one of the best examples of a mammalian gene controlled by oxygen tension. The DNA elements responsible for hypoxia-induced transcription consist of a short region of the proximal promoter and a <50-bp 3' enhancer. The elements act cooperatively to increase the transcriptional initiation rate approximately 100-fold in response to low oxygen tension in Hep3B cells. Two distinct types of transactivating proteins have been demonstrated to bind the response elements in the human EPO enhancer in vitro: one shows hypoxia-inducible DNA binding activity, while the other activity binds DNA under normoxic and hypoxic conditions. We have investigated the DNA-protein interactions on the human EPO enhancer in living tissue culture cells that produce EPO in a regulated fashion (Hep3B) and in cells that do not express EPO under any conditions tested (HeLa). We have identified in vivo DNA-protein interactions on the control elements in the human EPO enhancer by ligation-mediated PCR technology. We show that the putative protein binding sites in the EPO enhancer are occupied in vivo under conditions of normoxia, hypoxia, and cobalt exposure in EPO-producing cells. These sites are not occupied in cells that do not produce EPO. We also provide evidence for a conformational change in the topography of the EPO enhancer in response to hypoxia and cobalt exposure.

Sign in / Sign up

Export Citation Format

Share Document