{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T09:46:55Z","timestamp":1766137615930,"version":"3.41.2"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:p>A leading cause of lameness in modern broilers is bacterial chondronecrosis with osteomyelitis (BCO). While it is known that the components of BCO are bacterial infection, necrosis, and inflammation, the mechanism behind BCO etiology is not yet fully understood. In numerous species, including chicken, mitochondrial dysfunction has been shown to have a role in the pathogenicity of numerous diseases. The mitochondria is a known target for intracellular bacterial infections, similar to that of common causative agents in BCO, as well as a known regulator of cellular metabolism, stress response, and certain types of cell death. This study aimed to determine the expression profile of genes involved in mitochondrial biogenesis, dynamics, and function. RNA was isolated form the tibias from BCO-affected and healthy broilers and used to measure target gene expression via real-time qPCR. Mitochondrial biogenesis factors PGC-1\u03b1 and PGC-1\u03b2 were both significantly upregulated in BCO along with mitochondrial fission factors OMA1, MTFR1, MTFP1, and MFF1 as well as cellular respiration-related genes FOXO3, FOXO4, and av-UCP. Conversely, genes involved in mitochondrial function, ANT, COXIV, and COX5A showed decreased mRNA levels in BCO-affected tibia. This study is the first to provide evidence of potential mitochondrial dysfunction in BCO bone and warrants further mechanistic investigation into how this dysfunction contributes to BCO etiology.<\/jats:p>","DOI":"10.3389\/fvets.2021.640901","type":"journal-article","created":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T05:05:31Z","timestamp":1612155931000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Evidence of Mitochondrial Dysfunction in Bacterial Chondronecrosis With Osteomyelitis\u2013Affected Broilers"],"prefix":"10.3389","volume":"8","author":[{"given":"Alison","family":"Ferver","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Greene","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Wideman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sami","family":"Dridi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2365","DOI":"10.1017\/S1751731119000466","article-title":"Lameness and its relationship with health and production measures in broiler chickens","volume":"10","author":"Granquist","year":"2019","journal-title":"Animal."},{"key":"B2","doi-asserted-by":"publisher","first-page":"325","DOI":"10.3382\/ps\/pev320","article-title":"Bacterial chondronecrosis with osteomyelitis and lameness in broilers: a review","volume":"95","author":"Wideman","year":"2016","journal-title":"Poult Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"870","DOI":"10.3382\/ps.2011-01907","article-title":"A wire-flooring model for inducing lameness in broilers: evaluation of probiotics as a prophylactic treatment","volume":"91","author":"Wideman","year":"2012","journal-title":"Poult Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"183","DOI":"10.3389\/fendo.2012.00183","article-title":"Bone circulatory disturbances in the development of spontaneous bacterial chondronecrosis with osteomyelitis: a translational model for the pathogenesis of femoral head necrosis","volume":"3","author":"Wideman","year":"2012","journal-title":"Front Endocrinol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"25882","DOI":"10.1038\/srep25882","article-title":"An investigation into blood microbiota and its potential association with bacterial chondronecrosis with osteomyelitis (BCO) in Broilers","volume":"6","author":"Mandal","year":"2016","journal-title":"Sci Rep."},{"key":"B6","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3382\/ps\/peu025","article-title":"Prophylactic administration of a combined prebiotic and probiotic, or therapeutic administration of enrofloxacin, to reduce the incidence of bacterial chondronecrosis with osteomyelitis in broilers","volume":"1","author":"Wideman","year":"2015","journal-title":"Poult Sci."},{"key":"B7","first-page":"329","article-title":"Iron loaded chitooligosaccharide nanoparticles reduces incidence of bacterial chondronecrosis with osteomyelitis in broiler chickens","volume":"2","author":"Yousefi","year":"2019","journal-title":"Iran J Appl Anim Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.yexmp.2006.09.008","article-title":"Mitochondrial dysfunction and molecular pathways of disease","volume":"83","author":"Pieczenik","year":"2007","journal-title":"Exp Mol Pathol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"3117","DOI":"10.1172\/JCI22684","article-title":"Staphylococcus aureus panton-valentine leukocidin directly targets mitochondria and induces Bax-independent apoptosis of human neutrophils","volume":"115","author":"Genestier","year":"2005","journal-title":"J Clin Investig."},{"key":"B10","doi-asserted-by":"publisher","first-page":"3038","DOI":"10.1038\/emboj.2012.170","article-title":"Mitochondrial dysfunction in Parkinson's disease: molecular mechanisms and pathophysiological consequences","volume":"31","author":"Exner","year":"2012","journal-title":"EMBO J."},{"key":"B11","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1089\/ars.2009.2531","article-title":"Mitochondrial dysfunction in diabetes: from molecular mechanisms to functional significance and therapeutic opportunities","volume":"12","author":"Sivitz","year":"2010","journal-title":"Antioxid Redox Signal."},{"key":"B12","doi-asserted-by":"publisher","first-page":"S103","DOI":"10.2337\/diabetes.53.2007.S103","article-title":"Mitochondrial diabetes: molecular mechanisms and clinical presentation","volume":"53","author":"Maassen","year":"2004","journal-title":"Diabetes."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2077","DOI":"10.1016\/j.ajpath.2019.06.013","article-title":"Double-stranded RNA Is a novel molecular target in osteomyelitis pathogenesis: a translational avian model for human bacterial chondronecrosis with osteomyelitis","volume":"10","author":"Greene","year":"2019","journal-title":"Am J Pathol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/1472-6750-12-5","article-title":"An improved method for isolation of RNA from bone","volume":"12","author":"Carter","year":"2012","journal-title":"BMC Biotechnol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"R173","DOI":"10.1152\/ajpregu.00394.2014","article-title":"Orexin system is expressed in avian muscle cells and regulates mitochondrial dynamics","volume":"308","author":"Lassiter","year":"2015","journal-title":"AM J Physiol Reg I."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative C(T) method","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat Protocols."},{"key":"B17","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.mito.2013.01.003","article-title":"Mitochondrial dysfunction and the inflammatory response","volume":"13","author":"L\u00f3pez-Armada","year":"2013","journal-title":"Mitochondrion."},{"key":"B18","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.tcb.2020.01.006","article-title":"Mitochondrial Functions in Infection and Immunity","volume":"30","author":"Tiku","year":"2020","journal-title":"Trends Cell Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"e0205480","DOI":"10.1371\/journal.pone.0205480","article-title":"Further investigation of mitochondrial biogenesis and gene expression of key regulators in ascites- susceptible and ascites- resistant broiler research lines","volume":"14","author":"Al-Zahrani","year":"2019","journal-title":"PLOS ONE."},{"key":"B20","doi-asserted-by":"crossref","DOI":"10.5772\/intechopen.85177","article-title":"Orexin system and avian muscle mitochondria","volume-title":"Muscle Cells - Recent Advances and Future Prespectives","author":"Lassiter","year":"2020"},{"key":"B21","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1164\/rccm.200701-161OC","article-title":"Mitochondrial biogenesis restores oxidative metabolism during Staphylococcus aureus sepsis","volume":"176","author":"Haden","year":"2007","journal-title":"Am J Resp Crit Care."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1016\/j.bbamcr.2010.09.019","article-title":"Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network","volume":"1813","author":"Scarpulla","year":"2011","journal-title":"BBA Mol Cell Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1093\/cvr\/cvn098","article-title":"Transcriptional control of mitochondrial biogenesis: the central role of PGC-1\u03b1","volume":"79","author":"Ventura-Clapier","year":"2008","journal-title":"Cardiovasc Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1089\/ars.2014.6200","article-title":"Regulation of mitochondrial biogenesis and its intersection with inflammatory responses","volume":"22","author":"Cherry","year":"2015","journal-title":"Antioxid Redox Sign."},{"key":"B25","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1146\/annurev.physiol.010908.163119","article-title":"Transcriptional control of mitochondrial biogenesis and function","volume":"71","author":"Hock","year":"2009","journal-title":"Annu Rev Physiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1097\/CCM.0000000000003681","article-title":"Peripheral blood mononuclear cells demonstrate mitochondrial damage clearance during sepsis","volume":"47","author":"Kraft","year":"2019","journal-title":"Crit Care Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"10093","DOI":"10.2147\/CMAR.S211292","article-title":"ssbp1 upregulation in colorectal cancer regulates mitochondrial mass","volume":"11","author":"Yang","year":"2019","journal-title":"Cancer Manag Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"26185","DOI":"10.1074\/jbc.M503062200","article-title":"Disruption of fusion results in mitochondrial heterogeneity and dysfunction","volume":"280","author":"Chen","year":"2005","journal-title":"J Biol Chem."},{"key":"B29","doi-asserted-by":"publisher","first-page":"15927","DOI":"10.1073\/pnas.0407043101","article-title":"OPA1 requires mitofusin 1 to promote mitochondrial fusion","volume":"101","author":"Cipolat","year":"2004","journal-title":"Proc Natl Acad Sci USA."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1126\/science.1219855","article-title":"Mitochondrial fission, fusion, and stress","volume":"337","author":"Youle","year":"2012","journal-title":"Science."},{"key":"B31","doi-asserted-by":"publisher","first-page":"e50973","DOI":"10.7554\/eLife.50973","article-title":"Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner-membrane","volume":"9","author":"Ge","year":"2020","journal-title":"eLife."},{"key":"B32","doi-asserted-by":"publisher","first-page":"F1318","DOI":"10.1152\/ajprenal.00036.2014","article-title":"OMA1 mediates OPA1 proteolysis and mitochondrial fragmentation in experimental models of ischemic kidney injury","volume":"306","author":"Xiao","year":"2014","journal-title":"Am J Physiol Renal."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e2007","DOI":"10.1038\/cddis.2015.348","article-title":"NFAT4-dependent miR-324-5p regulates mitochondrial morphology and cardiomyocyte cell death by targeting Mtfr1","volume":"6","author":"Wang","year":"2015","journal-title":"Cell Death Dis."},{"key":"B34","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1016\/j.molcel.2017.08.013","article-title":"mTOR controls mitochondrial dynamics and cell survival via MTFP1","volume":"67","author":"Morita","year":"2017","journal-title":"Mol Cell."},{"key":"B35","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1091\/mbc.e13-09-0525","article-title":"Mutations in Fis1 disrupt orderly disposal of defective mitochondria","volume":"25","author":"Shen","year":"2013","journal-title":"Mol Biol Cell."},{"key":"B36","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1002\/cbin.11278","article-title":"MTFP1 overexpression promotes the growth of oral squamous cell carcinoma by inducing ROS production","volume":"44","author":"Xiao","year":"2020","journal-title":"Cell Biol Int."},{"key":"B37","doi-asserted-by":"publisher","first-page":"31544","DOI":"10.1074\/jbc.M404704200","article-title":"Knockdown of MTP18, a novel phosphatidylinositol 3-kinase-dependent protein, affects mitochondrial morphology and induces apoptosis","volume":"279","author":"Tondera","year":"2004","journal-title":"J Biol Chem."},{"key":"B38","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.bbadis.2005.07.001","article-title":"The relevance of mitochondrial membrane topology to mitochondrial function","volume":"1762","author":"Mannella","year":"2006","journal-title":"BBA Mol Basis Dis."},{"key":"B39","doi-asserted-by":"publisher","first-page":"2160","DOI":"10.1016\/j.tiv.2013.08.009","article-title":"Dibenzofuran-induced mitochondrial dysfunction: Interaction with ANT carrier","volume":"27","author":"Duarte","year":"2013","journal-title":"Toxicol Vitro."},{"key":"B40","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1016\/j.bbabio.2010.10.008","article-title":"Adenine nucleotide translocase 2 is a key mitochondrial protein in cancer metabolism","volume":"1807","author":"Chevrollier","year":"2011","journal-title":"BBA Bioenergetics."},{"key":"B41","doi-asserted-by":"publisher","first-page":"10486","DOI":"10.1021\/nn302457v","article-title":"Single-walled carbon nanotubes alter cytochrome c electron transfer and modulate mitochondrial function","volume":"6","author":"Ma","year":"2012","journal-title":"ACS Nano."},{"key":"B42","doi-asserted-by":"publisher","first-page":"110747","DOI":"10.1016\/j.cbpa.2020.110747","article-title":"Regulation of avian uncoupling protein (av-UCP) expression by cytokines and hormonal signals in quail myoblast cells","volume":"248","author":"Ferver","year":"2020","journal-title":"Comp Biochem Phys A."},{"key":"B43","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.taap.2006.01.003","article-title":"Diabetes and mitochondrial function: Role of hyperglycemia and oxidative stress","volume":"212","author":"Rolo","year":"2006","journal-title":"Toxicol Appl Pharm."},{"key":"B44","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1038\/cdd.2011.179","article-title":"FOXO3a regulates reactive oxygen metabolism by inhibiting mitochondrial gene expression","volume":"19","author":"Ferber","year":"2012","journal-title":"Cell Death Differ."},{"key":"B45","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1007\/s10863-017-9705-0","article-title":"Role of FOXO transcription factors in crosstalk between mitochondria and the nucleus","volume":"49","author":"Kim","year":"2017","journal-title":"J Bioenerg Biomembr."},{"key":"B46","doi-asserted-by":"publisher","first-page":"7403230","DOI":"10.1155\/2016\/7403230","article-title":"PPARs and mitochondrial metabolism: from NAFLD to HCC","volume":"2016","author":"Mello","year":"2016","journal-title":"PPAR Res."},{"key":"B47","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s12929-016-0309-5","article-title":"PPARs modulate cardiac metabolism and mitochondrial function in diabetes","volume":"24","author":"Lee","year":"2017","journal-title":"J Biomed Sci."}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2021.640901\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T05:05:34Z","timestamp":1612155934000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2021.640901\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,1]]},"references-count":47,"alternative-id":["10.3389\/fvets.2021.640901"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2021.640901","relation":{},"ISSN":["2297-1769"],"issn-type":[{"type":"electronic","value":"2297-1769"}],"subject":[],"published":{"date-parts":[[2021,2,1]]},"article-number":"640901"}}