Earlier proteoglycan turnover promotes higher efficiency matrix remodeling in MRL/MpJ tendons.
Earlier proteoglycan turnover promotes higher efficiency matrix remodeling in MRL/MpJ tendons.
复制标题
较早的蛋白多糖周转可促进 MRL/MpJ 肌腱中更高效率的基质重塑。
DOI：
10.1002/jor.25542
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Connizzo,BrianneK
中科院分区：
文献类型：
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作者：
Aggouras,AnthonyN;Connizzo,BrianneK
虽然大多数哺乳动物的组织再生能力有限，但墨菲罗斯大型 (MRL/MpJ) 小鼠已被确定可以再生多种组织，包括肌腱。最近的研究表明，这种再生反应是肌腱组织固有的，不依赖于全身炎症反应。因此，我们假设 MRL/MpJ 小鼠也可能对肌腱结构响应机械负荷表现出更强大的稳态调节。为了评估这一点，将 MRL/MpJ 和 C57BL/6J 指长屈肌腱外植体置于体外应力剥夺条件下长达 14 天。定期评估外植体肌腱的健康状况（代谢、生物合成和组成）、基质金属蛋白酶（MMP）活性、基因表达和肌腱生物力学。我们发现 MRL/MpJ 肌腱外植体对机械刺激的丧失有更强烈的反应，表现出胶原蛋白生成和 MMP 活性的增加，与之前的体内研究一致。在这种更大的胶原蛋白周转之前，富含亮氨酸的小蛋白聚糖和蛋白聚糖降解 MMP-3 的早期表达，促进了新合成胶原蛋白的有效调节和组织，并允许 MRL/MpJ 肌腱中更有效的整体周转。因此，MRL/MpJ 基质稳态的机制可能与 B6 肌腱的机制根本不同，并且可能表明 MRL/MpJ 肌腱的机械微损伤具有更好的恢复能力。我们在这里展示了 MRL/MpJ 模型在阐明有效基质周转机制方面的实用性，及其揭示新目标的潜力，以更有效地治疗由损伤、疾病或衰老引起的退行性基质变化。
While most mammalian tissue regeneration is limited, the Murphy Roths Large (MRL/MpJ) mouse has been identified to regenerate several tissues, including tendon. Recent studies have indicated that this regenerative response is innate to the tendon tissue and not reliant on a systemic inflammatory response. Therefore, we hypothesized that MRL/MpJ mice may also exhibit a more robust homeostatic regulation of tendon structure in response to mechanical loading. To assess this, MRL/MpJ and C57BL/6J flexor digitorum longus tendon explants were subjected to stress‐deprived conditions in vitro for up to 14 days. Explant tendon health (metabolism, biosynthesis, and composition), matrix metalloproteinase (MMP) activity, gene expression, and tendon biomechanics were assessed periodically. We found a more robust response to the loss of mechanical stimulus in the MRL/MpJ tendon explants, exhibiting an increase in collagen production and MMP activity consistent with previous in vivo studies. This greater collagen turnover was preceded by an early expression of small leucine‐rich proteoglycans and proteoglycan‐degrading MMP‐3, promoting efficient regulation and organization of newly synthesized collagen and allowing for more efficient overall turnover in MRL/MpJ tendons. Therefore, mechanisms of MRL/MpJ matrix homeostasis may be fundamentally different from that of B6 tendons and may indicate better recovery from mechanical microdamage in MRL/MpJ tendons. We demonstrate here the utility of the MRL/MpJ model in elucidating mechanisms of efficient matrix turnover and its potential to shed light on new targets for more effective treatments for degenerative matrix changes brought about by injury, disease, or aging.