Lamellar cell death and proliferation are associated with restricted ambulation and preferential weight bearing in a model relevant to supporting-limb laminitis.

IF 1.4 3区 农林科学 Q2 VETERINARY SCIENCES American journal of veterinary research Pub Date : 2025-02-19 Print Date: 2025-04-01 DOI:10.2460/ajvr.24.09.0268
Julie B Engiles, Darko Stefanovski, Andrew van Eps
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Abstract

Objective: To examine the effects of prolonged preferential weight bearing (PWB) and reduced ambulation (RA) on hoof lamellae using a nonpainful in vivo experimental model.

Methods: 12 healthy Standardbred horses were housed in stocks continuously for 92 hours. A platform shoe was placed on 1 forelimb in the PWB group (n = 6) to increase the load on the supporting limb (SL) by approximately 10% bodyweight, whereas the RA group (n = 6) had normal weight bearing. Archived healthy horse (n = 8) samples were used as controls. Histomorphometry and histochemistry (terminal deoxynucleotidyl transferase dUTP nick-end labeling [TUNEL], caspase-3, and targeting protein for Xenopus kinesin-like protein [TPX-2]) results were analyzed using mixed-effects linear regression.

Results: Lesions in multiple limbs from the PWB and RA groups included secondary epidermal lamellae elongation, cell death (mostly TUNEL-positive, caspase-3-negative parabasal keratinocytes), and basal cell proliferation (TPX-2 positive). Lesions were most severe in the PWB group SL, with significant increases (vs control) in mean (95% CI) primary epidermal lamellar (PEL) length (3.7 [95% CI, 3.5 to 3.8] mm vs 3.2 [95% CI, 2.9 to 3.4] mm; P < .001), secondary epidermal lamellae length (281 [95% CI, 235 to 327] µm vs 185 [95% CI, 155 to 215] µm; P < .001), TUNEL count (45 [95% CI, 30 to 60] vs 4 [95% CI, 2 to 5] positive cells/PEL; P < .001), and TPX-2 count (116 [95% CI, 46 to 186] vs 5 [95% CI, 3 to 6] positive cells/PEL; P < .002). Both TUNEL- and TPX-2-positive cell counts were increased in the RA group forelimbs versus control (P < .05).

Conclusions: Restriction of normal ambulation, even in the absence of increased weight bearing, caused lamellar parabasal keratinocyte death and structural derangement of lamellae.

Clinical relevance: Promoting ambulation, not just limb load relief, may be a critical strategy for preventing SL laminitis.

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在一个与支肢板板炎相关的模型中,板层细胞死亡和增殖与受限活动和优先负重有关。
目的:采用无痛动物实验模型,研究长时间优先负重(PWB)和减少步行(RA)对蹄片的影响。方法:12匹健康的标准种马,连续饲养92小时。PWB组(n = 6)在1条前肢上放置平台鞋,以使支撑肢(SL)的负荷增加约10%体重,而RA组(n = 6)负重正常。以存档的健康马(n = 8)为对照。使用混合效应线性回归分析组织形态学和组织化学(末端脱氧核苷酸转移酶dUTP镍端标记[TUNEL]、caspase-3和Xenopus激酶样蛋白靶向蛋白[TPX-2])结果。结果:PWB组和RA组多肢病变包括继发性表皮片延长、细胞死亡(多为tunel阳性、caspase-3阴性的基底旁角质形成细胞)和基底细胞增殖(TPX-2阳性)。PWB组的病变最严重,与对照组相比,原发性表皮板层(PEL)平均(95% CI)长度显著增加(3.7 [95% CI, 3.5至3.8]mm vs 3.2 [95% CI, 2.9至3.4]mm;P < 0.001),次生表皮片长度(281 [95% CI, 235 ~ 327]µm vs 185 [95% CI, 155 ~ 215]µm;P < 0.001), TUNEL计数(45 [95% CI, 30 ~ 60] vs 4 [95% CI, 2 ~ 5]个阳性细胞/PEL;P < 0.001), TPX-2计数(116 [95% CI, 46 ~ 186]对5 [95% CI, 3 ~ 6]个阳性细胞/PEL;P < .002)。RA组前肢TUNEL-和tpx -2阳性细胞计数均高于对照组(P < 0.05)。结论:限制正常活动,即使体重没有增加,也会导致板层基底旁角化细胞死亡和板层结构紊乱。临床相关性:促进活动,而不仅仅是减轻肢体负荷,可能是预防SL板炎的关键策略。
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来源期刊
CiteScore
1.70
自引率
10.00%
发文量
186
审稿时长
3 months
期刊介绍: The American Journal of Veterinary Research supports the collaborative exchange of information between researchers and clinicians by publishing novel research findings that bridge the gulf between basic research and clinical practice or that help to translate laboratory research and preclinical studies to the development of clinical trials and clinical practice. The journal welcomes submission of high-quality original studies and review articles in a wide range of scientific fields, including anatomy, anesthesiology, animal welfare, behavior, epidemiology, genetics, heredity, infectious disease, molecular biology, oncology, pharmacology, pathogenic mechanisms, physiology, surgery, theriogenology, toxicology, and vaccinology. Species of interest include production animals, companion animals, equids, exotic animals, birds, reptiles, and wild and marine animals. Reports of laboratory animal studies and studies involving the use of animals as experimental models of human diseases are considered only when the study results are of demonstrable benefit to the species used in the research or to another species of veterinary interest. Other fields of interest or animals species are not necessarily excluded from consideration, but such reports must focus on novel research findings. Submitted papers must make an original and substantial contribution to the veterinary medicine knowledge base; preliminary studies are not appropriate.
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