Maturating Articular Cartilage Can Induce Ectopic Joint-Like Structures in Neonatal Mice
Maturating Articular Cartilage Can Induce Ectopic Joint-Like Structures in Neonatal Mice
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成熟的关节软骨可诱导新生小鼠异位关节样结构
DOI：
10.1007/s40883-020-00176-w
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发表时间：
2020
影响因子：
2.6
通讯作者：
T
中科院分区：
文献类型：
--
作者：
Miura;Shinichirou Tsutsumi;Rio Agata;Kiyokazu Endo;T
摘要骨关节炎给我们的社会带来了巨大的健康负担。为了寻找诱导本质上有限的关节软骨（AC）再生的潜在方法，我们专注于两个相对关节之间的相互作用。为了评估 AC 相对区域的相互作用对关节成熟的作用，我们在远端指间水平截肢，而不损伤中间指骨 (P2) 的关节面，并观察到 AC 的带状组织有缺陷。然后，我们在不损伤近节指骨（P1）关节面的情况下去除了 P2 骨，并在远端指间水平附近截肢了手指的剩余部分。 II 型胶原和蛋白聚糖 4 (PRG4) 的分布模式表明 P1 中 AC 的成熟被延迟。这两个实验表明，关节中相对的 AC 之间的相互作用对于新生儿手指中 AC 的带状组织的成熟是必要的。为了测试关节的相互作用是否足以诱发关节软骨，P2 的近端片段被切除、翻转并放回原来的位置。在倒置移植物的AC和P2远端部分的切割边缘之间的界面区域诱导新形成的软骨。 II 型胶原和 PRG4 在异位软骨中的表达方式与正常 AC 类似，表明新生 AC 可以在小鼠中诱导异位关节样结构，与在蝾螈和青蛙中报道的类似结构相当。这些结果表明，新生关节可能是 AC 再生的感应信号源。 总结在本研究中，我们通过实验证明新生小鼠似乎具有再生手指关节软骨 (AC) 的能力。众所周知，小鼠在截肢后可以再生指尖，但在更近端的截肢水平上不会再生。因此，人们认为哺乳动物的关节结构是不可再生的。然而，我们发现，当正常的手指 AC 放置在骨头切割边缘附近时，可以在非关节区域诱导类似 AC 的结构，这表明正常的 AC 在新生小鼠的某些情况下具有再生能力。未来的工作关节疾病是我们社会的一个巨大的健康问题。这项研究的结果表明，新生儿 AC 可能是 AC 再生的感应信号的潜在来源。这些感应信号的发现将有助于开发人类关节的再生疗法。
AbstractOsteoarthritis is a huge health burden to our society. Seeking for potential ways to induce regeneration of articular cartilage (AC) that is intrinsically limited, we focused on the interaction between two opposing joints. To evaluate the role of the interaction of opposing regions of AC for joint maturation, we amputated digits at the distal interphalangeal level without injuring the articular surface of the intermediate phalanx (P2) and observed that the zonal organization of AC was defective. We then removed the P2 bone without injuring the articular surface of the proximal phalanx (P1), and the remaining part of the digit was amputated near the distal interphalangeal level. The distribution pattern of type II collagen and proteoglycan 4 (PRG4) suggested that maturation of AC in P1 was delayed. These two experiments suggested that an interaction between the opposing AC in a joint is necessary for maturation of the zonal organization of AC in neonatal digits. To test if an interaction of the joints is sufficient to induce articular cartilage, a proximal fragment of P2 was resected, inverted, and put back into the original location. Newly formed cartilage was induced at the interface region between the AC of the inverted graft and the cut edge of the distal part of P2. Type II collagen and PRG4 were expressed in the ectopic cartilage in a similar manner to normal AC, indicating that neonatal AC can induce ectopic joint-like structures in mice comparable with what has been reported in newts and frogs. These results suggest that the neonatal joint could be a source of inductive signals for regeneration of AC.Lay SummaryIn this study, we experimentally show that neonatal mice appear to have the capacity to regenerate articular cartilage (AC) in digits. It is already known that mice can regenerate a digit tip after amputation, but do not regenerate in response to amputations at more proximal levels. Therefore, it has been thought that mammalian joint structures are non-regenerative. However, we found that normal digit AC can induce AC-like structures in a non-joint region when it is placed next to the cut edge of a bone, suggesting that the normal AC has regenerative capacity in certain situations in neonatal mice.Future WorksJoint disorders are a huge health problem of our society. The results of this study suggest that neonatal AC could be a potential source of inductive signals for regeneration of AC. The discovery of these inductive signals will aid in developing regenerative therapies of a joint in human.
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功能关节再生是使用爪诺邦Laevis中的重新整合机制实现的。
DOI：
10.1002/reg2.49
发表时间：
2016-02
期刊：
Regeneration (Oxford, England)
影响因子：
--
作者：
Tsutsumi R;Yamada S;Agata K
通讯作者：
Agata K
影响因子：
2.7
作者：
Endo, T;Bryant, SV;Gardiner, DM
通讯作者：
Gardiner, DM
影响因子：
2.1
作者：
Pacifici, Maurizio;Koyama, Eiki;Iwamoto, Masahiro
通讯作者：
Iwamoto, Masahiro
DOI：
10.1002/reg2.81
发表时间：
2017-06
期刊：
Regeneration (Oxford, England)
影响因子：
--
作者：
Dawson LA;Yu L;Yan M;Marrero L;Schanes PP;Dolan C;Pela M;Petersen B;Han M;Muneoka K
通讯作者：
Muneoka K
影响因子：
6.9
作者：
Decker, Rebekah S.;Koyama, Eiki;Pacifici, Maurizio
通讯作者：
Pacifici, Maurizio