Changes of bone remodeling, cartilage damage and apoptosis-related pathways in broilers with femoral head necrosis

doi:10.1016/j.jia.2024.03.084

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Yaling Yu, Hongfan Ge, Hang Gao, Yanyan Zhang, Kangping Liu, Zhenlei Zhou^#

Department of Veterinary Clinical Science, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China

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摘要【目的】股骨头坏死（femoral head necrosis, FHN）是家禽业中常见的一种腿部疾病，是现代肉鸡养殖业的潜在挑战。它通常会出现严重的软骨损伤，还会诱发肉鸡跛行，使其无法获得足够的食物和水。尽管已发现内质网应激（endoplasmic reticulum stress, ERS）在糖皮质激素诱导的FHN肉鸡中发挥作用，但导致软骨损伤的异常细胞凋亡的机制仍不清楚。【方法】在本研究中，从肉鸡养殖场中采集了患有股骨头分离（femoral head separation, FHS）和伴发生长板损伤的股骨头分离（femoral head separation accompanied with growth plate lacerations, FHSL）的肉鸡软骨样本。目的是研究FHN的严重程度与骨重塑和软骨损伤之间的潜在联系。此外，本实验还采用了甲泼尼龙（methylprednisolone, MP）处理肉鸡原代软骨细胞，以构建体外 FHN 模型。随后抑制或激活 ERS 通路或缺氧诱导因子1α（hypoxia inducible factor-1α, HIF-1α），进一步研究软骨细胞凋亡的潜在机制。【结果】尽管FHN肉鸡中与骨代谢有关的调节因子发生了显著变化，但只有 FHSL 肉鸡的骨质和生物力学受到了影响。而软骨损伤的程度与疾病的严重程度密切相关，因此软骨似乎是研究 FHN 潜在机制的合适组织。此外，FHN肉鸡软骨还表现出高水平的细胞凋亡，且ERS 通路相关基因和 HIF-1α 的表达水平上调。而MP处理软骨细胞后，软骨细胞凋亡增加，ERS 通路被过度激活，这与 FHN 肉鸡的结果类似。实验结果还显示，FHN肉鸡中高水平的HIF-1α，与FHN严重程度评分和软骨细胞凋亡率呈显著正相关。用 HIF-1α 或 ERS 抑制剂或激活剂处理软骨细胞后，结果被进一步验证了。【结论】总之，FHN 肉鸡的骨重塑和软骨稳态均受到影响，但只有软骨损伤会随着 FHN 的发展而显著加剧。此外，ERS通路或HIF-1α的激活会导致软骨细胞凋亡，因此它们与肉鸡FHN的严重程度有显著相关性。【创新性】该研究探究了骨重塑和软骨稳态与肉鸡FHN 的潜在联系，并为软骨损伤在FHN发生发展中的作用提供了更多依据。其次，进一步探索了与软骨细胞凋亡的ERS通路与HIF-1α在FHN中的作用机制，揭示了HIF-1α的水平与FHN严重程度间的紧密联系。这些研究结果为肉鸡 FHN 的早期诊断和干预提供有价值的见解。

Abstract Femoral head necrosis (FHN) is a common leg disorder in the poultry industry often leads to significant cartilage damage. The mechanism behind abnormal apoptosis in FHN broilers, leading to cartilage damage, remains unclear; although endoplasmic reticulum stress (ERS) has been found to play a role in glucocorticoid-induced FHN broilers. In this study, we collected samples from broilers with femoral head separation (FHS) and femoral head separation accompanied with growth plate lacerations (FHSL) in a broiler farm. The aim was to investigate the potential association between the severity of FHN, bone remodeling and cartilage damage. Additionally, primary chondrocytes were treated with methylprednisolone (MP) to construct an in vitro FHN model, followed by inhibition or activation of ERS or hypoxia inducible factor-1α (HIF-1α) to further investigate the mechanism of apoptosis in cartilage. The results suggested that cartilage appeared to be the appropriate tissue to investigate the potential mechanisms of FHN, as the degree of cartilage damage was found to be closely related to the severity of the disease. Bone quality was only affected in FHSL broilers, although factors related to bone metabolism were significantly altered among FHN-affected broilers. In addition, cartilage in FHN-affected broilers exhibited high levels of apoptosis and upregulated expression of ERS-related and HIF-1α, which was consistent with both in vivo and in vitro findings after MP treatment. The results were further supported by treatment with HIF-1α or ERS inhibition or activation. In conclusion, bone remodeling and cartilage homeostasis were affected in FHN broilers, but only cartilage damage was significantly exacerbated with FHN development. Moreover, activation of ERS or HIF-1α resulted in apoptosis in cartilage, thus exhibiting a significant correlation with FHN severity.

Keywords: femoral head necrosis bone remodeling cartilage homeostasis apoptosis-related pathways

Online: 26 April 2024

Fund: This work was supported by the National Natural Science Foundation of China (grant 32072936 and grant 32273080). And the fund was used for experimental research, purchase of consumables, personnel employment, result analysis and so on. The experiment was approved by the Animal Protection and Utilization Committee of Nanjing Agricultural University (approval #NJAU-Poult-2021110203, granted on 2 November 2021) and performed in accordance with the "Guidelines for Laboratory Animals" issued by the Ministry of Science and Technology (2006, Beijing, China). The authors would like to thank all the reviewers who participated in the review and MJEditor (www.mjeditor.com) for its linguistic assistance during the preparation of this manuscript.

About author: Yaling Yu, E-mail: 2020207037@stu.njau.edu.cn; #Correspondence Zhenlei Zhou, Tel: +86-25-8439-5505, E-mail: zhouzl@njau.edu.cn

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Yaling Yu, Hongfan Ge, Hang Gao, Yanyan Zhang, Kangping Liu, Zhenlei Zhou. 2024. Changes of bone remodeling, cartilage damage and apoptosis-related pathways in broilers with femoral head necrosis. Journal of Integrative Agriculture, Doi:10.1016/j.jia.2024.03.084

Akman M, Belisario D C, Salaroglio I C, Kopecka J, Donadelli M, De Smaele E, Riganti C. 2021. Hypoxia endoplasmic reticulum stress and chemoresistance: dangerous liaisons. Journal of Experimental & Clinical Cancer Research, 40.

Bartoszewska S, Collawn J F. 2020. Unfolded protein response (UPR) integrated signaling networks determine cell fate during hypoxia. Cellular & Molecular Biology Letters, 25.

Boss J H, Misselevich I. 2003. Osteonecrosis of the femoral head of laboratory animals: the lessons learned from a comparative study of osteonecrosis in man and experimental animals. Veterinary Pathology, 40, 345-354.

Charlier E, Relic B, Deroyer C, Malaise O, Neuville S, Collee J, De Seny D. 2016. Insights on Molecular Mechanisms of Chondrocytes Death in Osteoarthritis. International Journal of Molecular Sciences, 17.

Chevet E, Hetz C, Samali A. 2015. Endoplasmic reticulum stress-activated cell reprogramming in oncogenesis. Cancer Discovery, 5, 586-597.

Cook M E. 2000. Skeletal deformities and their causes: introduction. Poultry Science, 79, 982-984.

Cui Q, Wang G. J, Su C C, Balian G. 1997. The Otto Aufranc Award. Lovastatin prevents steroid induced adipogenesis and osteonecrosis. Clinical Orthopaedics and Related Ressearch, 344, 8-19.

Delbrel E, Soumare A, Naguez A, Label R, Bernard O, Bruhat A, Boncoeur E. 2018. HIF-1 alpha triggers ER stress and CHOP-mediated apoptosis in alveolar epithelial cells a key event in pulmonary fibrosis. Scientific Reports, 8.

Erken H. Y, Ofluoglu O, Aktas M, Topal C, Yildiz M. 2012. Effect of pentoxifylline on histopathological changes in steroid-induced osteonecrosis of femoral head: experimental study in chicken. International Orthopaedics, 36, 1523-1528.

Gao H, Zhang Y, Liu K, Fan R, Li Q, Zhou Z. 2022. Dietary sodium butyrate and/or vitamin D3 supplementation alters growth performance meat quality chemical composition and oxidative stability in broilers. Food Chem, 390, 133-138.

Havenstein G B, Ferket P R, Qureshi M A. 2003. Growth livability and feed conversion of 1957 versus 2001 broilers when fed representative 1957 and 2001 broiler diets. Poultry Science, 82, 1500-1508.

Hetz C, Bernasconi P, Fisher J, Lee A. H, Bassik M C, Antonsson B, Korsmeyer S J. 2006. Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1 alpha. Science, 312, 572-576.

Hetz C, Zhang K Z, Kaufman R J. 2020. Mechanisms regulation and functions of the unfolded protein response. Nature Reviews Molecular Cell Biology, 21, 421-438.

Huang Z W, Zhou M, Wang Q, Zhu M J, Chen S, Li H. 2017. Mechanical and hypoxia stress can cause chondrocytes apoptosis through over-activation of endoplasmic reticulum stress. Archives of Oral Biology, 84, 125-132.

Julian R J. 1998. Rapid growth problems: ascites and skeletal deformities in broilers. Poultry Science, 77, 1773-1780.

Julian R J. 2005. Production and growth related disorders and other metabolic diseases of poultry--a review. Veterinary Journal, 169, 350-369.

Kerachian M A, Seguin C, Harvey E J. 2009. Glucocorticoids in osteonecrosis of the femoral head: A new understanding of the mechanisms of action. Journal of Steroid Biochemistry and Molecular Biology, 114, 121-128.

Li W, Cao T, Luo C Y, Cai J L, Zho X P, Xiao X H, Liu S Q. 2020. Crosstalk between ER stress NLRP3 inflammasome and inflammation. Applied Microbiology and Biotechnology, 104, 6129-6140.

Liu Y J, Shan H J, Zong Y, Lin Y W, Xia W Y, Wang N, Yu X W. 2021. IKKe in osteoclast inhibits the progression of methylprednisolone-induced osteonecrosis. International Journal of Biological Sciences, 17, 1353-1360.

Ma Y J, Brewer J W, Diehl J A, Hendershot L M. 2002. Two distinct stress signaling pathways converge upon the CHOP promoter during the mammalian unfolded protein response. Journal of Molecular Biology, 318, 1351-1365.

McCullough K D, Martindale J L, Klotz L O, Aw T Y, Holbrook N J. 2001. Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state. Molecular and Cellular Biology, 21, 1249-1259.

McNamee P T, McCullagh J J, Thorp B H, Ball H J, Graham D, McCullough S J, Smyth J A. 1998. Study of leg weakness in two commercial broiler flocks. Veterinary Record, 143, 131-135.

McNamee P T, Smyth J A. 2000. Bacterial chondronecrosis with osteomyelitis ("femoral head necrosis") of broiler chickens: A review. Avian Pathology, 4, 253-270.

Namgaladze D, Khodzhaeva V, Brune B. 2019. ER-Mitochondria Communication in Cells of the Innate Immune System. Cells, 8.

Okada K, Mori D, Makii Y, Nakamoto H, Murahashi Y, Yano F, Saito T. 2020. Hypoxia-inducible factor-1 alpha maintains mouse articular cartilage through suppression of NF-kappa B signaling. Scientific Reports, 10.

Okazaki S, Nishitani Y, Nagoya S, Kaya M, Yamashita T, Matsumoto H. 2009. Femoral head osteonecrosis can be caused by disruption of the systemic immune response via the toll-like receptor 4 signalling pathway. Rheumatology (Oxford), 48, 227-232.

Olkowski A A, Laarveld B, Wojnarowicz C, Chirino-Trejo M, Chapman D, Wysokinski T W, Quaroni L. 2011. Biochemical and physiological weaknesses associated with the pathogenesis of femoral bone degeneration in broiler chickens. Avian Pathology, 40, 639-650.

Oppong E, Cato A C. 2015. Effects of Glucocorticoids in the Immune System. Advances in Experimental Medicine and Biology, 872, 217-233.

Packialakshmi B, Liyanage R, Lay J, Jr, Okimoto R, Rath N. 2015. Prednisolone-induced predisposition to femoral head separation and the accompanying plasma protein changes in chickens. Biomark Insights, 10, 1-8.

Packialakshmi B, Rath N C, Huff W E, Huff G R. 2015. Poultry Femoral Head Separation and Necrosis: A Review. Avian Diseases, 59, 349-354.

Raehtz S, Hargis B. M, Kuttappan V A, Pamukcu R, Bielke L R, McCabe L R. 2018. High Molecular Weight Polymer Promotes Bone Health and Prevents Bone Loss Under Salmonella Challenge in Broiler Chickens. Frontiers in Physiology, 9, 384.

Rellmann Y, Eidhof E, Dreier R. 2021. Review: ER stress-induced cell death in osteoarthritic cartilage. Cellular Signalling, 78.

Riddell C, Springer R. 1985. An epizootiological study of acute death syndrome and leg weakness in broiler chickens in western Canada. Avian Diseases, 29, 90-102.

Sandell L J, Aigner T. 2001. Articular cartilage and changes in arthritis. An introduction: cell biology of osteoarthritis. Arthritis Research, 3, 107-113.

Schonthal A H. 2013. Pharmacological targeting of endoplasmic reticulum stress signaling in cancer. Biochemical Pharmacology, 85, 653-666.

Schroder M, Kaufman R J. 2005. ER stress and the unfolded protein response. Mutation Research: International Journal on Mutagenesis, Chromosome Breakage and Related Subjects, 569, 29-63.

Shim M Y, Pesti G M. 2011. Effects of incubation temperature on the bone development of broilers. Poultry Science, 90,1867-1877.

Singh B. 2000. Stimulation of the developing immune system can prevent autoimmunity. Journal of Autoimmunity, 14, 15-22.

Stegen S, Laperre K, Eelen G, Rinaldi G, Fraisl P, Torrekens S, Carmeliet G. 2019. HIF-1 alpha metabolically controls collagen synthesis and modification in chondrocytes. Nature, 565, 511-+.

Tang J Y, Jin P, He Q, Lu L H, Ma J P, Gao W L, Yang J. 2017. Naringenin ameliorates hypoxia/reoxygenation-induced endoplasmic reticulum stress-mediated apoptosis in H9c2 myocardial cells: involvement in ATF6 IRE1 alpha and PERK signaling activation. Molecular and Cellular Biochemistry, 424, 111-122.

Thorp B H, Ducro B, Whitehead C C, Farquharson C, Sorensen P. 1993. Avian tibial dyschondroplasia: the interaction of genetic selection and dietary 125-dihydroxycholecalciferol. Avian Pathology, 22, 311-324.

Urano F, Wang X Z, Bertolotti A, Zhang Y H, Chung P, Harding H P, Ron D. 2000. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science, 287, 664-666.

Wideman R F Jr, Pevzner I. 2012. Dexamethasone triggers lameness associated with necrosis of the proximal tibial head and proximal femoral head in broilers. Poultry Science, 91, 2464-2474.

Yang N, Sun H Y, Xue Y, Zhang W C, Wang H Z, Tao H Q, Geng D C. 2021. Inhibition of MAGL activates the Keap1/Nrf2 pathway to attenuate glucocorticoid-induced osteonecrosis of the femoral head. Clinical and Translational Medicine, 11.

Yu Y L, Lin L S, Liu K P, Jiang Y X, Zhou Z L. 2022. Effects of Simvastatin on Cartilage Homeostasis in Steroid-Induced Osteonecrosis of Femoral Head by Inhibiting Glucocorticoid Receptor. Cells, 11.

Yu Y L, Wang S J, Zhou Z L. 2020. Cartilage Homeostasis Affects Femoral Head Necrosis Induced by Methylprednisolone in Broilers. International Journal of Molecular Sciences, 21.

Zhang F J, Luo W, Lei G H. 2015. Role of HIF-1 alpha and HIF-2 alpha in osteoarthritis. Joint Bone Spine, 82,144-147.

Zhang M, Li S W, Pang K Y, Zhou Z L. 2019. Endoplasmic reticulum stress affected chondrocyte apoptosis in femoral head necrosis induced by glucocorticoid in broilers. Poultry Science, 98, 1111-1120.

Zhang M, Shi C Y, Zhou Z L, Hou J F. 2017. Bone characteristics histopathology and chondrocyte apoptosis in femoral head necrosis induced by glucocorticoid in broilers. Poultry Science, 96, 1609-1614.

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