FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Oxid Med Cell Longev / Macroautophagy and Selective Mitophagy Ameliorate Chondrogen...
Oxidative medicine and cellular longevity2016; 2016; 3718468; doi: 10.1155/2016/3718468

Macroautophagy and Selective Mitophagy Ameliorate Chondrogenic Differentiation Potential in Adipose Stem Cells of Equine Metabolic Syndrome: New Findings in the Field of Progenitor Cells Differentiation.

Abstract: Equine metabolic syndrome (EMS) is mainly characterized by insulin resistance, obesity, and local or systemic inflammation. That unfriendly environment of adipose tissue has huge impact on stem cells population (ASC) residing within. In the present study, using molecular biology techniques and multiple imaging techniques (SEM, FIB-SEM, and confocal microscopy), we evaluated the impact of EMS on ASC viability and chondrogenic differentiation. Moreover, we visualized the mitochondrial network and dynamics in ASC and ASC during control and chondrogenic conditions. In control conditions, ASC were characterized by increased mitochondrial fission in comparison to ASC. We found that extensive remodeling of mitochondrial network including fusion and fission occurs during early step of differentiation. Moreover, we observed mitochondria morphology deterioration in ASC. These conditions seem to cause autophagic shift in ASC, as we observed increased accumulation of LAMP2 and formation of multiple autophagosomes in those cells, some of which contained dysfunctional mitochondria. "Autophagic" switch may be a rescue mechanism allowing ASC to clear impaired by ROS proteins and mitochondria. Moreover it provides a precursors-to-macromolecules synthesis, especially during chondrogenesis. Our data indicates that autophagy in ASC would be crucial for the quality control mechanisms and maintenance of cellular homeostasis ASC allowing them to be in "stemness" status.
Get Full Text
Publication Date: 2016-12-08 PubMed ID: 28053691PubMed Central: PMC5178365DOI: 10.1155/2016/3718468Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research studies the effects of equine metabolic syndrome (EMS) on the viability and chondrogenic differentiation of adipose stem cells (ASC) in horses, highlighting mitochondrial dynamics and autophagy mechanisms as significant factors in maintaining stem cell health.

Understanding the Impact of EMS

  • This study is rooted in the exploration of Equine Metabolic Syndrome (EMS), a disorder in horses that’s predominantly characterized by insulin resistance, obesity, and local or systemic inflammation. The researchers were primarily interested in how this disease affects stem cell populations within adipose tissue.
  • Observations suggested that EMS deteriorates the living environment for stem cells, potentially disrupting their viability and differentiation into chondrocytes (cells that are integral for cartilage formation).

Exploring ASC Viability and Chondrogenic Differentiation

  • Molecular biology techniques and multiple imaging techniques were employed to determine how EMS impacts the viability and chondrogenic differentiation of adipose stem cells (ASC).
  • Observations of mitochondrial dynamics during the experiments suggested considerable remodeling of the mitochondrial network, with increased fission in comparison to healthy ASC. Fusion and fission activities were detected, primarily during the early stages of differentiation. Morphological deterioration of the mitochondria was also noted in ASC from EMS-afflicted subjects.

Role of Autophagy in ASC Health

  • The study found increased accumulation of LAMP2 along with multiple autophagosomes formations in the EMS-stricken ASC. These autophagosomes were seen to contain dysfunctional mitochondria.
  • The researchers propose this autophagy switch might offer a rescue mechanism that allows ASC to clear proteins and mitochondria impaired by reactive oxygen species (ROS).
  • The study suggests that autophagy may also provide precursors for macromolecule synthesis during chondrogenesis – the process of cartilage formation.
  • The findings propose that autophagy mechanisms could be vital for quality control and maintenance of cellular homeostasis among ASC and that it could help these stem cells retain their “stemness” status.

Cite This Article

APA
Marycz K, Kornicka K, Grzesiak J, Śmieszek A, Szłapka J. (2016). Macroautophagy and Selective Mitophagy Ameliorate Chondrogenic Differentiation Potential in Adipose Stem Cells of Equine Metabolic Syndrome: New Findings in the Field of Progenitor Cells Differentiation. Oxid Med Cell Longev, 2016, 3718468. https://doi.org/10.1155/2016/3718468

Publication

Oxidative medicine and cellular longevity
ISSN: 1942-0994
NlmUniqueID: 101479826
Country: United States
Language: English
Volume: 2016
Pages: 3718468
PII: 3718468

Researcher Affiliations

Marycz, Krzysztof
  • Electron Microscopy Laboratory, The Faculty of Biology and Animal Science, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland; Wroclaw Research Centre EIT+, Wroclaw, Poland.
Kornicka, Katarzyna
  • Electron Microscopy Laboratory, The Faculty of Biology and Animal Science, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland; Wroclaw Research Centre EIT+, Wroclaw, Poland.
Grzesiak, Jakub
  • Wroclaw Research Centre EIT+, Wroclaw, Poland.
Śmieszek, Agnieszka
  • Electron Microscopy Laboratory, The Faculty of Biology and Animal Science, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland.
Szłapka, Jolanta
  • Electron Microscopy Laboratory, The Faculty of Biology and Animal Science, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland.

MeSH Terms

  • Adipose Tissue / pathology
  • Animals
  • Autophagy / genetics
  • Cell Differentiation / genetics
  • Cell Proliferation / genetics
  • Cell Shape / genetics
  • Cells, Cultured
  • Chondrocytes / metabolism
  • Chondrocytes / pathology
  • Chondrogenesis / genetics
  • Endoplasmic Reticulum Stress / genetics
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation
  • Horses
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Immunophenotyping
  • Male
  • Metabolic Syndrome / genetics
  • Metabolic Syndrome / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Mitochondria / metabolism
  • Mitophagy / genetics
  • Multipotent Stem Cells / metabolism
  • Multipotent Stem Cells / pathology
  • Nitric Oxide / metabolism
  • Reactive Oxygen Species / metabolism
  • Stem Cells / metabolism
  • Stem Cells / pathology
  • Superoxide Dismutase / metabolism

Conflict of Interest Statement

The authors declare that there is no conflict of interests.

References

This article includes 48 references
  1. Frank N. Equine metabolic syndrome. Journal of Equine Veterinary Science 2009;29(5):259–267.
    doi: 10.1016/j.jevs.2009.04.183google scholar: lookup
  2. Hashemian SJ, Kouhnavard M, Nasli-Esfahani E. Mesenchymal Stem Cells: Rising Concerns over Their Application in Treatment of Type One Diabetes Mellitus.. J Diabetes Res 2015;2015:675103.
    doi: 10.1155/2015/675103pmc: PMC4630398pubmed: 26576437google scholar: lookup
  3. Pileggi A. Mesenchymal stem cells for the treatment of diabetes.. Diabetes 2012 Jun;61(6):1355-6.
    doi: 10.2337/db12-0355pmc: PMC3357279pubmed: 22618774google scholar: lookup
  4. Kita K, Gauglitz GG, Phan TT, Herndon DN, Jeschke MG. Isolation and characterization of mesenchymal stem cells from the sub-amniotic human umbilical cord lining membrane.. Stem Cells Dev 2010 Apr;19(4):491-502.
    doi: 10.1089/scd.2009.0192pubmed: 19635009google scholar: lookup
  5. Ratajczak J, Wysoczynski M, Hayek F, Janowska-Wieczorek A, Ratajczak MZ. Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication.. Leukemia 2006 Sep;20(9):1487-95.
    doi: 10.1038/sj.leu.2404296pubmed: 16791265google scholar: lookup
  6. Marycz K, Grzesiak J, Wrzeszcz K, Golonka P. Adipose stem cell combined with plasma-based implant bone tissue differentiation in vitro and in a horse with a phalanx digitalis distalis fracture: a case report. Veterinarni Medicina 2012;57(11):610–617.
  7. Grzesiak J, Krzysztof M, Karol W, Joanna C. Isolation and morphological characterisation of ovine adipose-derived mesenchymal stem cells in culture.. Int J Stem Cells 2011 Nov;4(2):99-104.
    doi: 10.15283/ijsc.2011.4.2.99pmc: PMC3840966pubmed: 24298341google scholar: lookup
  8. Tropel P, Noël D, Platet N, Legrand P, Benabid AL, Berger F. Isolation and characterisation of mesenchymal stem cells from adult mouse bone marrow.. Exp Cell Res 2004 May 1;295(2):395-406.
    doi: 10.1016/j.yexcr.2003.12.030pubmed: 15093739google scholar: lookup
  9. McClelland AD, Kantharidis P. microRNA in the development of diabetic complications.. Clin Sci (Lond) 2014 Jan;126(2):95-110.
    doi: 10.1042/cs20130079pubmed: 24059587google scholar: lookup
  10. Marycz K, Kornicka K, Basinska K, Czyrek A. Equine Metabolic Syndrome Affects Viability, Senescence, and Stress Factors of Equine Adipose-Derived Mesenchymal Stromal Stem Cells: New Insight into EqASCs Isolated from EMS Horses in the Context of Their Aging.. Oxid Med Cell Longev 2016;2016:4710326.
    doi: 10.1155/2016/4710326pmc: PMC4670679pubmed: 26682006google scholar: lookup
  11. Glick D, Barth S, Macleod KF. Autophagy: cellular and molecular mechanisms.. J Pathol 2010 May;221(1):3-12.
    doi: 10.1002/path.2697pmc: PMC2990190pubmed: 20225336google scholar: lookup
  12. Ding WX, Yin XM. Mitophagy: mechanisms, pathophysiological roles, and analysis.. Biol Chem 2012 Jul;393(7):547-64.
    doi: 10.1515/hsz-2012-0119pmc: PMC3630798pubmed: 22944659google scholar: lookup
  13. Marędziak M, Marycz K, Lewandowski D, Siudzińska A, Śmieszek A. Static magnetic field enhances synthesis and secretion of membrane-derived microvesicles (MVs) rich in VEGF and BMP-2 in equine adipose-derived stromal cells (EqASCs)-a new approach in veterinary regenerative medicine.. In Vitro Cell Dev Biol Anim 2015 Mar;51(3):230-40.
    doi: 10.1007/s11626-014-9828-0pmc: PMC4368852pubmed: 25428200google scholar: lookup
  14. Collino F, Deregibus MC, Bruno S, Sterpone L, Aghemo G, Viltono L, Tetta C, Camussi G. Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs.. PLoS One 2010 Jul 27;5(7):e11803.
    doi: 10.1371/journal.pone.0011803pmc: PMC2910725pubmed: 20668554google scholar: lookup
  15. Ratajczak MZ. Microvesicles as immune orchestra conductors.. Blood 2008 May 15;111(10):4832-3.
    doi: 10.1182/blood-2008-02-136028pmc: PMC2384118pubmed: 18467599google scholar: lookup
  16. Ratajczak J, Miekus K, Kucia M, Zhang J, Reca R, Dvorak P, Ratajczak MZ. Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery.. Leukemia 2006 May;20(5):847-56.
    doi: 10.1038/sj.leu.2404132pubmed: 16453000google scholar: lookup
  17. Xu D, Tahara H. The role of exosomes and microRNAs in senescence and aging.. Adv Drug Deliv Rev 2013 Mar;65(3):368-75.
    doi: 10.1016/j.addr.2012.07.010pubmed: 22820533google scholar: lookup
  18. Basinska K, Marycz K, Śieszek A, Nicpoń J. The production and distribution of IL-6 and TNF-a in subcutaneous adipose tissue and their correlation with serum concentrations in Welsh ponies with equine metabolic syndrome.. J Vet Sci 2015;16(1):113-20.
    doi: 10.4142/jvs.2015.16.1.113pmc: PMC4367141pubmed: 25269712google scholar: lookup
  19. Knott G, Rosset S, Cantoni M. Focussed ion beam milling and scanning electron microscopy of brain tissue.. J Vis Exp 2011 Jul 6;(53):e2588.
    doi: 10.3791/2588pmc: PMC3196160pubmed: 21775953google scholar: lookup
  20. Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.. Anal Biochem 1987 Apr;162(1):156-9.
    doi: 10.1016/0003-2697(87)90021-2pubmed: 2440339google scholar: lookup
  21. Shin H, Han C, Labuz JM, Kim J, Kim J, Cho S, Gho YS, Takayama S, Park J. High-yield isolation of extracellular vesicles using aqueous two-phase system.. Sci Rep 2015 Aug 14;5:13103.
    doi: 10.1038/srep13103pmc: PMC4536486pubmed: 26271727google scholar: lookup
  22. Klinker MW, Wei CH. Mesenchymal stem cells in the treatment of inflammatory and autoimmune diseases in experimental animal models.. World J Stem Cells 2015 Apr 26;7(3):556-67.
    doi: 10.4252/wjsc.v7.i3.556pmc: PMC4404391pubmed: 25914763google scholar: lookup
  23. Kang HS, Liao G, DeGraff LM, Gerrish K, Bortner CD, Garantziotis S, Jetten AM. CD44 plays a critical role in regulating diet-induced adipose inflammation, hepatic steatosis, and insulin resistance.. PLoS One 2013;8(3):e58417.
    doi: 10.1371/journal.pone.0058417pmc: PMC3591334pubmed: 23505504google scholar: lookup
  24. Liu LF, Kodama K, Wei K, Tolentino LL, Choi O, Engleman EG, Butte AJ, McLaughlin T. The receptor CD44 is associated with systemic insulin resistance and proinflammatory macrophages in human adipose tissue.. Diabetologia 2015 Jul;58(7):1579-86.
    doi: 10.1007/s00125-015-3603-ypubmed: 25952479google scholar: lookup
  25. Deiuliis JA. MicroRNAs as regulators of metabolic disease: pathophysiologic significance and emerging role as biomarkers and therapeutics.. Int J Obes (Lond) 2016 Jan;40(1):88-101.
    doi: 10.1038/ijo.2015.170pmc: PMC4722234pubmed: 26311337google scholar: lookup
  26. Xu J, Wu W, Zhang L, Dorset-Martin W, Morris MW, Mitchell ME, Liechty KW. The role of microRNA-146a in the pathogenesis of the diabetic wound-healing impairment: correction with mesenchymal stem cell treatment.. Diabetes 2012 Nov;61(11):2906-12.
    doi: 10.2337/db12-0145pmc: PMC3478555pubmed: 22851573google scholar: lookup
  27. Fisher FM, Chui PC, Antonellis PJ, Bina HA, Kharitonenkov A, Flier JS, Maratos-Flier E. Obesity is a fibroblast growth factor 21 (FGF21)-resistant state.. Diabetes 2010 Nov;59(11):2781-9.
    pmc: PMC2963536pubmed: 20682689doi: 10.2337/db10-0193google scholar: lookup
  28. Zhang X, Yeung DC, Karpisek M, Stejskal D, Zhou ZG, Liu F, Wong RL, Chow WS, Tso AW, Lam KS, Xu A. Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans.. Diabetes 2008 May;57(5):1246-53.
    pubmed: 18252893doi: 10.2337/db07-1476google scholar: lookup
  29. Mendelsohn AR, Larrick JW. Fibroblast growth factor-21 is a promising dietary restriction mimetic.. Rejuvenation Res 2012 Dec;15(6):624-8.
    doi: 10.1089/rej.2012.1392pubmed: 23173578google scholar: lookup
  30. Wall CE, Whyte J, Suh JM, Fan W, Collins B, Liddle C, Yu RT, Atkins AR, Naviaux JC, Li K, Bright AT, Alaynick WA, Downes M, Naviaux RK, Evans RM. High-fat diet and FGF21 cooperatively promote aerobic thermogenesis in mtDNA mutator mice.. Proc Natl Acad Sci U S A 2015 Jul 14;112(28):8714-9.
    doi: 10.1073/pnas.1509930112pmc: PMC4507233pubmed: 26124126google scholar: lookup
  31. Marycz K, Kornicka K, Marędziak M, Golonka P, Nicpoń J. Equine metabolic syndrome impairs adipose stem cells osteogenic differentiation by predominance of autophagy over selective mitophagy.. J Cell Mol Med 2016 Dec;20(12):2384-2404.
    doi: 10.1111/jcmm.12932pmc: PMC5134411pubmed: 27629697google scholar: lookup
  32. Martin SD, McGee SL. The role of mitochondria in the aetiology of insulin resistance and type 2 diabetes.. Biochim Biophys Acta 2014 Apr;1840(4):1303-12.
    doi: 10.1016/j.bbagen.2013.09.019pubmed: 24060748google scholar: lookup
  33. Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI. Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes.. N Engl J Med 2004 Feb 12;350(7):664-71.
    doi: 10.1056/nejmoa031314pmc: PMC2995502pubmed: 14960743google scholar: lookup
  34. Mizushima N, Levine B. Autophagy in mammalian development and differentiation.. Nat Cell Biol 2010 Sep;12(9):823-30.
    doi: 10.1038/ncb0910-823pmc: PMC3127249pubmed: 20811354google scholar: lookup
  35. Behrends C, Sowa ME, Gygi SP, Harper JW. Network organization of the human autophagy system.. Nature 2010 Jul 1;466(7302):68-76.
    doi: 10.1038/nature09204pmc: PMC2901998pubmed: 20562859google scholar: lookup
  36. Mizushima N, Komatsu M. Autophagy: renovation of cells and tissues.. Cell 2011 Nov 11;147(4):728-41.
    doi: 10.1016/j.cell.2011.10.026pubmed: 22078875google scholar: lookup
  37. Phadwal K, Watson AS, Simon AK. Tightrope act: autophagy in stem cell renewal, differentiation, proliferation, and aging.. Cell Mol Life Sci 2013 Jan;70(1):89-103.
    doi: 10.1007/s00018-012-1032-3pmc: PMC3535400pubmed: 22669258google scholar: lookup
  38. Zhang Q, Yang YJ, Wang H, Dong QT, Wang TJ, Qian HY, Xu H. Autophagy activation: a novel mechanism of atorvastatin to protect mesenchymal stem cells from hypoxia and serum deprivation via AMP-activated protein kinase/mammalian target of rapamycin pathway.. Stem Cells Dev 2012 May 20;21(8):1321-32.
    doi: 10.1089/scd.2011.0684pmc: PMC3353754pubmed: 22356678google scholar: lookup
  39. Oliver L, Hue E, Priault M, Vallette FM. Basal autophagy decreased during the differentiation of human adult mesenchymal stem cells.. Stem Cells Dev 2012 Oct 10;21(15):2779-88.
    doi: 10.1089/scd.2012.0124pubmed: 22519885google scholar: lookup
  40. Takano-Ohmuro H, Mukaida M, Kominami E, Morioka K. Autophagy in embryonic erythroid cells: its role in maturation.. Eur J Cell Biol 2000 Oct;79(10):759-64.
    doi: 10.1078/0171-9335-00096pubmed: 11089924google scholar: lookup
  41. Zhang Y, Goldman S, Baerga R, Zhao Y, Komatsu M, Jin S. Adipose-specific deletion of autophagy-related gene 7 (atg7) in mice reveals a role in adipogenesis.. Proc Natl Acad Sci U S A 2009 Nov 24;106(47):19860-5.
    doi: 10.1073/pnas.0906048106pmc: PMC2785257pubmed: 19910529google scholar: lookup
  42. Bohensky J, Shapiro IM, Leshinsky S, Terkhorn SP, Adams CS, Srinivas V. HIF-1 regulation of chondrocyte apoptosis: induction of the autophagic pathway.. Autophagy 2007 May-Jun;3(3):207-14.
    doi: 10.4161/auto.3708pubmed: 17224629google scholar: lookup
  43. Ogata M, Hino S, Saito A, Morikawa K, Kondo S, Kanemoto S, Murakami T, Taniguchi M, Tanii I, Yoshinaga K, Shiosaka S, Hammarback JA, Urano F, Imaizumi K. Autophagy is activated for cell survival after endoplasmic reticulum stress.. Mol Cell Biol 2006 Dec;26(24):9220-31.
    doi: 10.1128/MCB.01453-06pmc: PMC1698520pubmed: 17030611google scholar: lookup
  44. Kouroku Y, Fujita E, Tanida I, Ueno T, Isoai A, Kumagai H, Ogawa S, Kaufman RJ, Kominami E, Momoi T. ER stress (PERK/eIF2alpha phosphorylation) mediates the polyglutamine-induced LC3 conversion, an essential step for autophagy formation.. Cell Death Differ 2007 Feb;14(2):230-9.
    doi: 10.1038/sj.cdd.4401984pubmed: 16794605google scholar: lookup
  45. Cho DH, Nakamura T, Lipton SA. Mitochondrial dynamics in cell death and neurodegeneration.. Cell Mol Life Sci 2010 Oct;67(20):3435-47.
    doi: 10.1007/s00018-010-0435-2pubmed: 20577776google scholar: lookup
  46. Joshi A, Kundu M. Mitophagy in hematopoietic stem cells: the case for exploration.. Autophagy 2013 Nov 1;9(11):1737-49.
    doi: 10.4161/auto.26681pmc: PMC4028333pubmed: 24135495google scholar: lookup
  47. Forni MF, Peloggia J, Trudeau K, Shirihai O, Kowaltowski AJ. Murine Mesenchymal Stem Cell Commitment to Differentiation Is Regulated by Mitochondrial Dynamics.. Stem Cells 2016 Mar;34(3):743-55.
    doi: 10.1002/stem.2248pmc: PMC4803524pubmed: 26638184google scholar: lookup
  48. Craft AM, Ahmed N, Rockel JS, Baht GS, Alman BA, Kandel RA, Grigoriadis AE, Keller GM. Specification of chondrocytes and cartilage tissues from embryonic stem cells.. Development 2013 Jun;140(12):2597-610.
    doi: 10.1242/dev.087890pubmed: 23715552google scholar: lookup

Citations

This article has been cited 36 times.
Subscribe to our newsletter
Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.