Factors secreted from dental pulp stem cells show multifaceted benefits for treating experimental temporomandibular joint osteoarthritis
Factors secreted from dental pulp stem cells show multifaceted benefits for treating experimental temporomandibular joint osteoarthritis
复制标题
DOI：
10.1016/j.joca.2020.03.010
复制
发表时间：
2020-06-01
影响因子：
7
通讯作者：
Yamamoto, A.
中科院分区：
文献类型：
--
作者：
Ogasawara, N.;Kano, F.;Yamamoto, A.
目的：颞下颌关节骨关节炎（TMJOA）是一种以进行性软骨退变、骨重建异常和慢性疼痛为特征的退行性疾病。在这项研究中，我们的目的是研究有效的治疗方法，以扭转或抑制TMJOA progress.Design：为此，我们进行静脉注射无血清条件培养基从人类脱落乳牙干细胞（SHED-CM）到机械应力诱导的小鼠TMJOA模型。SHED-CM给药显著抑制颞肌炎症，并且改善了骨的完整性和被破坏的髁突软骨的表面光滑度。此外，SHED-CM治疗减少了表达IL-1 β、iNOS和MMP-13的软骨细胞的数量，而它特异性地增加了多能多形细胞层中的PCNA阳性细胞。值得注意的是，在SHED-CM处理的髁突中TdT介导的dUTP缺口末端标记（TUNEL）阳性凋亡软骨细胞的数量显著低于用DMEM处理的那些，而蛋白多糖阳性区域恢复到与假处理组相似的水平，表明SHED-CM处理再生了机械应力损伤的髁突软骨和软骨下骨。分泌组学分析表明，SHED-CM包含多种治疗因子，作用于骨软骨再生。结论：我们的数据表明，SHED-CM治疗促进机械应力诱导的小鼠TMJOA的再生和修复。我们的观察结果表明，SHED-CM有可能成为一种有效的组织再生治疗剂，用于重度TMJOA患者。(C)2020年国际骨关节炎研究学会。由爱思唯尔有限公司出版。保留所有权利。
Objective: Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease characterized by progressive cartilage degeneration, abnormal bone remodeling, and chronic pain. In this study, we aimed to investigate effective therapies to reverse or suppress TMJOA progression.Design: To this end, we performed intravenous administration of serum free conditioned media from human exfoliated deciduous teeth stem cells (SHED-CM) into a mechanical-stress induced murine TMJOA model.Results: SHED-CM administration markedly suppressed temporal muscle inflammation, and improved bone integrity and surface smoothness of the destroyed condylar cartilage. Moreover, SHED-CM treatment decreased the number of IL-1 beta, iNOS, and MMP-13 expressing chondrocytes, whereas it specifically increased PCNA-positive cells in the multipotent polymorphic cell layer. Notably, the numbers of TdT-mediated dUTP nick end labeling (TUNEL)-positive apoptotic chondrocytes in the SHED-CM treated condyles were significantly lower than in those treated with DMEM, whereas the proteoglycan positive area was restored to a level similar to that of the sham treated group, demonstrating that SHED-CM treatment regenerated the mechanical-stress injured condylar cartilage and subchondral bone. Secretome analysis revealed that SHED-CM contained multiple therapeutic factors that act in osteochondral regeneration.Conclusions: Our data demonstrated that SHED-CM treatment promoted the regeneration and repair of mechanical-stress induced mouse TMJOA. Our observations suggest that SHED-CM has potential to be a potent tissue-regenerating therapeutic agent for patients with severe TMJOA. (C) 2020 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.