BMP-2 functional polypeptides relieve osteolysis via bi-regulating bone formation and resorption coupled with macrophage polarization.
BMP-2 functional polypeptides relieve osteolysis via bi-regulating bone formation and resorption coupled with macrophage polarization.
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BMP - 2功能多肽通过双向调节骨形成与骨吸收并结合巨噬细胞极化来缓解骨质溶解。
DOI：
10.1038/s41536-023-00279-2
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发表时间：
2023-02-09
影响因子：
7.2
通讯作者：
Shi, Qin
中科院分区：
文献类型：
--
作者：
Wang, Jiaqian;Xue, Yuan;Wang, Yi;Liu, Chang;Hu, Sihan;Zhao, Huan;Gu, Qiaoli;Yang, Huilin;Huang, Lixin;Zhou, Xichao;Shi, Qin
假体周围磨损碎片引起的骨溶解是无菌性松动的主要原因。延长假肢的使用寿命仍然具有挑战性。在本研究中，我们首先合成了骨形态发生蛋白2（BMP-2）功能性多肽（BMP2pp），并在体外评估了BMP2pp对巨噬细胞极化和钛（Ti）颗粒引起的成骨受损的影响。然后，我们在钛颗粒诱导的小鼠颅骨骨溶解模型中描述了 BMP2pp 对骨形成和骨吸收的影响。结果表明，BMP2pp不仅可以减轻Ti诱导的人胎盘源性间充质干细胞（hPMSCs）成骨细胞分化的抑制，而且可以阻止Ti诱导的M1巨噬细胞极化并促进小鼠M2巨噬细胞分化。来自 BMP2pp 激活巨噬细胞的条件培养基增加了 hPMSC 的成骨作用。蛋白质印迹结果表明，用 BMP2pp 处理的骨髓源性巨噬细胞中 NF-κB 诱导激酶 (NIK) 和磷酸化 NF-κB p65 的表达显着降低。此外，我们还阐明了 BMP2pp 对小鼠骨形成和骨吸收减少的保护作用以及颅骨骨溶解的免疫调节特性。总之，BMP2pp 改善了 Ti 介导的 hPMSC 成骨潜力损伤，通过抑制 NF-κB 信号通路的激活抑制巨噬细胞的 M1 极化，并改善 Ti 诱导的骨溶解。我们的研究表明，BMP2pp 可能是治疗假体磨损碎片引起的假体松动的潜在选择。
Osteolysis caused by wear debris around the prosthesis is the main reason for aseptic loosening. Extending prosthetic service life is still challenging. In this study, we first synthesized a bone morphogenetic protein-2 (BMP-2) functional polypeptide (BMP2pp), and evaluated the effects of BMP2pp on macrophage polarization and impaired osteogenesis caused by titanium (Ti) particles in vitro. Then, we delineated the impact of BMP2pp on bone formation and resorption in a mouse calvarial bone osteolysis model induced by Ti particles. The results showed that BMP2pp not only alleviated the Ti-induced inhibition of osteoblastic differentiation in human placenta-derived mesenchymal stem cells (hPMSCs) but also prevented Ti-induced M1 macrophage polarization and promoted M2 macrophage differentiation in mice. Conditioned medium from BMP2pp-activated macrophages increased the osteogenesis of hPMSCs. The western blot results indicated a significant decrease in the expression of NF-κB inducing kinase (NIK) and phospho-NF-κB p65 in bone marrow-derived macrophages treated with BMP2pp. Furthermore, we clarified the protective effect of BMP2pp on bone formation and the reduction in bone resorption coupled with the immunomodulatory properties of calvarial osteolysis in mice. In summary, BMP2pp ameliorated the Ti-mediated impairment in osteogenic potential of hPMSCs, suppressed the M1 polarization of macrophages by inhibiting the activation of the NF-κB signaling pathway, and ameliorated Ti-induced bone osteolysis. Our research suggests that BMP2pp may be a potential option for treating prosthetic loosening induced by wear debris from prostheses.
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巨噬细胞和骨炎症
影响因子：
6.6
作者：
Gu Q;Yang H;Shi Q
通讯作者：
Shi Q
影响因子：
29
作者：
Bouhlel, M. Amine;Derudas, Bruno;Chinetti-Gbaguidi, Giulia
通讯作者：
Chinetti-Gbaguidi, Giulia
影响因子：
4.6
作者：
Cho, Untack;Kim, Boyun;Song, Yong Sang
通讯作者：
Song, Yong Sang
影响因子：
4
作者：
Jensen, Eric D.;Pham, Lan;Billington, Charles J., Jr.;Espe, Kelly;Carlson, Ann E.;Westendorf, Jennifer J.;Petryk, Anna;Gopalakrishnan, Rajaram;Mansky, Kim
通讯作者：
Mansky, Kim
DOI：
10.1002/jbm.a.36504
发表时间：
2018-10
期刊：
Journal of biomedical materials research. Part A
影响因子：
--
作者：
Lin T;Kohno Y;Huang JF;Romero-Lopez M;Pajarinen J;Maruyama M;Nathan K;Yao Z;Goodman SB
通讯作者：
Goodman SB