Micro-Injury of the Tendon-Bone Junction Caused by Acute Exhaustive Exercise in Rats: Ultrastructural Changes and Mechanism

Xiao-ping Shui; Hao-Nan Wang; Chun-ying Li; Xin Zhang; Bin Li

doi:10.3791/69184

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Research Article

Micro-Injury of the Tendon-Bone Junction Caused by Acute Exhaustive Exercise in Rats: Ultrastructural Changes and Mechanism

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DOI:

10.3791/69184

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November 14th, 2025

Xiao-ping Shui¹^,² , Hao-Nan Wang³^,⁴ , Chun-ying Li⁵ , Xin Zhang⁶ , Bin Li²

¹Department of Rehabilitation, Sichuan college of traditional Chinese medicine, ²Department of Rehabilitation, Mian-yang Orthopedic hospital, ³Sports Medicine Center, West China Hospital, Sichuan University, ⁴Department of Orthopedics and Orthopedic Research Institute, West China Hospital, ⁵Department of Geriatric Medicine, Mian-yang hospital of traditional Chinese medicine, ⁶Department of Rehabilitation Medicine, Sichuan Provincial Orthopedic Hospital

Corresponding Authors: Hao-Nan Wang <haonanwang@aliyun.com>

Summary

This study aimed to explore the ultrastructural changes and mechanisms at the tendon-bone junction due to acute exhaustive exercise. Acute exhaustive exercise induces micro-injury at the tendon-bone junction, transiently activating ER stress and its mediated apoptotic signaling pathways. Nevertheless, these micro-injuries and ER stress can be progressively restored post-exercise.

Abstract

Exercise-induced micro-injuries at the tendon-bone junction (enthesis) can lead to tendinopathy. Investigating the ultrastructural changes and mechanisms within the enthesis following acute exhaustive exercise can improve our understanding of tendinopathy and guide clinical treatments. In this study, thirty-six male Sprague-Dawley rats were randomly assigned to two groups: control and exhaustive exercise. The exhaustive exercise group was further subdivided into five subgroups based on the time post-exercise: 0 h, 6 h, 12 h, 24 h, and 48 h. Hematoxylin-eosin staining and electron microscopy were employed to examine changes in the calcaneal tendon-bone junction. The expression of endoplasmic reticulum stress (ERS)-related proteins GRP78, CHOP, and Caspase-12 at the tendon-bone junction was quantified using immunohistochemistry (IHC). Following acute exhaustive exercise, the tendon-bone junctions of rats that underwent exhaustive exercise displayed significant structural alterations. Chondrocytes and collagen fibers exhibited notable ultrastructural changes indicative of ERS. ERS protein levels increased immediately after exercise, peaking at 6 h. These protein levels began to decline at 12 h post-exercise and returned to baseline by 48 h. In conclusion, acute exhaustive exercise induces micro-damage and endoplasmic reticulum stress at the tendon-bone junction in rats, but no irreversible damage ensues. Timely treatment and repair of these micro-injuries can prevent excessive damage and the development of tendinopathy.

Introduction

Achilles tendinopathy is a common clinical condition caused by frequent ankle overuse injuries. This disorder is characterized by tendon swelling, pain, and dysfunction. It is more prevalent in older individuals and athletes, particularly runners and jumpers. Achilles tendinopathy is categorized into non-insertional and insertional tendinopathy. Non-insertional tendinopathy affects the tendon 2 to 6 cm above its bone insertion, while insertional tendinopathy affects the tendon-bone junction¹. Moreover, non-insertional tendinopathy tends to occur in overweight, older, and less active persons, whereas insertional tendinopathy tends to occur in mo....