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

doi:10.1016/j.jia.2024.03.084

Journal of Integrative Agriculture

2026, Vol. 25

Issue (2): 788-802 DOI: 10.1016/j.jia.2024.03.084

Animal Science · Veterinary Medicine

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

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

Highlights
● Although regulatory factors related to bone remodeling are changed in all broilers with femoral head necrosis, significant changes in bone biomechanics occur only when severe femoral head necrosis (femoral head separation with growth plate lacerations) occurs.
● The severity of femoral head necrosis and the level of HIF-1α are both closely associated with cartilage damage and apoptosis in broilers.

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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

Received: 13 October 2023 Accepted: 20 February 2024 Online: 29 March 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, E-mail: zhouzl@njau.edu.cn

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