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Treadmill running exercise results in the presence of numerous myofibroblasts in mouse patellar tendons

热1 Dr.LinZhen 添加于 2011-1-12 15:55 | 3548 次阅读 | 5 个评论

作者
Szczodry M, Zhang J, Lim C, Davitt HL, Yeager T, Fu FH, Wang JH-C
摘要
Mechanical loading is known to alter tendon structure, but its cellular mechanisms are unclear. This study aimed to determine the effect of mechanical loading on tendon cells in vivo. C57BL/6J female mice were used in a treadmill running study. The treadmill running protocol consisted of treadmill training for 1 week, followed by sustained moderate running at 13 m/min for 50 min/day, 5 days/week, for 3 weeks. Immunohistochemical staining of tendon sections of mice after treadmill running revealed that numerous cells in the tendon section expressed alpha-SMA, whereas in the tendon sections of control mice, only a few cells exhibited weak alpha-SMA signals. Furthermore, mouse patellar tendon cells (MPTCs) derived from treadmill running mice were generally larger in culture, proliferated faster, expressed a higher level of alpha-SMA, and formed more abundant stress fibers compared to MPTCs from control mice. In addition, MPTCs from treadmill running mice generated larger traction forces (169 +/- 66.1 Pa) than those from control mice (102 +/- 34.2 Pa). Finally, cells from treadmill running mice produced higher levels of total collagen (516.4 +/- 92.7 microg/10,000 cells) than their counterparts (303.9 +/- 34.8 microg/10,000 cells). Thus, mechanical loading via treadmill running increased the presence of myofibroblasts in mouse patellar tendons. As myofibroblasts are activated fibroblasts, their presence in the tendon following treadmill running indicates that they actively repair and remodel tendon tissue under strenuous mechanical loading, leading to known changes in tendon structure.
详细资料
- 文献种类:期刊
- 期刊名称: Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
- 期刊缩写: J Orthop Res
- 期卷页: 2009年第27卷第10期 1373-1378页
- 地址: MechanoBiology Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- ISBN: 0736-0266
- 备注:PMID:19350660
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My email to the author:

We are working on a project that is going to use treadmill running system to create tendinopathy model on mice. I read from your paper published in JOR that treadmill running actually enhances tendon in mice, which is contradicted to rat as previously reported. And you also mention in the other paper that PGE2 was elevated and the tendon might be at the "healing" stage after the running program (13 m/min for 50 min/day, 5 days/week, for 3 weeks). I am just wondering whether you have applied a longer running program on mice which would eventually develop tendinopathy.

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!reply! Dr.LinZhen 2011-1-13 10:16: The author's reply:

The answer is probably yes, as we have now found that prolonged intensive treadmill running elevates non-tenocyte related gene expression. I will report our findings in the ISL&T today.

!reply! dr.qinan 2011-1-13 13:08: it is an interesting report. So what does this mean to you?

!reply! Dr.LinZhen 2011-1-13 13:18: dr.qinan: it is an interesting report. So what does this mean to you?
Regular exercise is good for muscle and tendon training, but intensive exercise or overuse would still very likely cause damage. I think the "enhanced tendon" is a compensation effect. But a preliminary study is necessary to confirm.

!reply! Dr.LinZhen 2011-1-13 13:44: The author's report in ISL&T

INTENSIVE MECHANICAL LOADING CONTAINS THE RISK OF DEVELOPING TENDINOPATHY
Jianying Zhang, James H-C. Wang#
MechanoBiology Laboratory, Departments of Orthopaedic Surgery and Bioengineering
University of Pittsburgh, Pittsburgh, PA, #wanghc@pitt.edu
INTRODUCTION
Mechanical loading has been considered to play a major role in the development of tendinopathy, which is characterized by the presence of lipid deposition, increased amounts of proteoglycans, and calcified tissue in the affected tendon [1,2]. These histopathological findings suggest that tendon cells may be able to undergo aberrant differentiation such that non-tendinous tissues are formed in the tendons in response to excessive mechanical loading placed on them. Therefore, this study aims to test the hypothesis that moderate mechanical loading produces anabolic responses from the tendon in terms of increasing expression of tendon-related genes, whereas excessive mechanical loading induces expression of genes related to nontendinous tissues. To test this hypothesis, we used mouse treadmill running as an experimental model.
MATERIALS AND METHODS
A total of 18 C57BL/6J female mice (2.5 months old) were divided into three groups: moderate treadmill running group (MTR), intensive treadmill running group (ITR), and cage control group, with 6 mice in each group. In the first week, all 12 mice in both the MTR and ITR groups received training for treadmill running at 13 m/min, 15 min/days, and 5 days/week. Following this training period, mice in the MTR group ran at the same speed for 50 min/day, 5 days/week, and 3 weeks total. On the other hand, mice in the ITR group ran at the same speed for 3 hr/day, 4 hr/day, and 5 hr/day for 5 days in the second, third, and fourth weeks, respectively. The control group remained in cages with free movement during treadmill running experiments. After the end of treadmill running, mice were sacrificed, and their patellar tendon (PT) and Achilles tendon (AT) tissue samples were harvested for gene expression analysis using real time qRT-PCR. A t-test was used for statistical analysis,
with p < 0.05 being considered significantly different.
Fig. 1 MTR upregulated
collagen type I and
tenomodulin gene expression in
mouse patellar tendon (A) and
Achilles tendon (B). Nontendinous
tissue related genes
however were not affected. (*p
< 0.05).
Fig. 2 ITR increased expression
of genes related to nontendinous
tissues in addition to
elevating tendon-related gene
expression in both the patellar
tendon (A) and Achilles tendon
(B). (*p < 0.05).
RESULTS
We found that for both PTs and ATs in the MTR group, tendon-related genes, including collagen type I (Coll. I) and tenomodulin (Tenom.) were markedly upregulated, but genes related to non-tendinous tissues, LPL (fatty tissue), SOX9(cartilage), and Runx2 and osterix (bony tissue), were not affected (Fig. 1). However, in the ITR group, all genes related to non-tendinous tissues in both PTs and ATs were highly expressed in addition to high levels of tendon-related gene expression
(Fig. 2).
RESULTS
The results of this study support our working hypothesis. They show that while moderate mechanical loading on tendons may be beneficial in terms of upregulating collagen type I and tenomodulin gene expression, intensive mechanical loading could be detrimental as it induces expression of non-tendinous tissue related genes. The highly expressed genes correspond to the tissue phenotypes found in tendinopathic tendons [1, 2]. Therefore, long term, intensive mechanical loading may eventually
lead to degenerative changes (lipids, proteoglycan accumulation, and calcification) in the tendon tissue. Moreover, we suspect that tendon stem cells (TSCs) [3] are responsible for the upregulation of non-tendinous tissue related gene expression, as TSCs are known to express genes related to non-tenocytes in vitro [4].
References: [1] Kannus and Jozsa, 1991;[2] Tallon et al., 2001; [3] Zhang and Wang, 2010; [4] Zhang and Wang, 2010.
Acknowledgement: This work was supported in part by NIH AR049921 and AR049921S2 (JHW).