Collagen-like Osteoclast-Associated Receptor (OSCAR)-Binding Motifs Show a Co-Stimulatory Effect on Osteoclastogenesis in a Peptide Hydrogel System.
Collagen-like Osteoclast-Associated Receptor (OSCAR)-Binding Motifs Show a Co-Stimulatory Effect on Osteoclastogenesis in a Peptide Hydrogel System.
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胶原样破骨细胞相关的受体（奥斯卡）结合基序对肽水凝胶系统中的骨质构成显示出共刺激作用。
DOI：
10.3390/ijms25010445
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发表时间：
2023-12-28
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
破骨细胞生成是骨重建的动力学途径之一，是一个包括多个阶段的复杂过程。这种复杂性虽然提供了丰富的治疗机会，但在揭示潜在机制方面存在重大挑战。因此，有一个强大的模型系统，以了解破骨细胞生成的高需求。水凝胶接种破骨细胞前体和装饰肽或蛋白质模仿骨的细胞外基质可以提供一个有用的合成工具，研究破骨细胞前基质的相互作用和它们对破骨细胞的影响。例如，纤维状胶原蛋白已显示通过与破骨细胞相关受体（OSCAR）相互作用为破骨细胞生成提供共刺激途径，OSCAR是在破骨细胞前体细胞表面上表达的破骨细胞生成的调节剂。基于这个基本原理，我们设计了两个OSCAR结合肽和一个重组OSCAR结合蛋白，并将它们与肽基水凝胶结合，研究它们对破骨细胞生成的影响。通过圆二色谱法和表面等离子体共振分析表明，OSCAR结合肽具有胶原蛋白三螺旋构象并与OSCAR相互作用。此外，它们对破骨细胞生成具有积极作用，如破骨细胞形成的典型基因表达和抗酒石酸酸性磷酸酶染色所证明的。当与未修饰的水凝胶相比时，OSCAR结合肽或OSCAR结合重组蛋白与基于肽的水凝胶的组合增强破骨细胞分化，如通过多成核和通过显示特征性破骨细胞样形态的F-肌动蛋白染色所证明的。我们设想，这些水凝胶可用作研究破骨细胞生成的平台，特别是，调查涉及OSCAR的共刺激途径的影响。
Osteoclastogenesis, one of the dynamic pathways underlying bone remodelling, is a complex process that includes many stages. This complexity, while offering a wealth of therapeutic opportunities, represents a substantial challenge in unravelling the underlying mechanisms. As such, there is a high demand for robust model systems to understand osteoclastogenesis. Hydrogels seeded with osteoclast precursors and decorated with peptides or proteins mimicking bone’s extracellular matrix could provide a useful synthetic tool to study pre-osteoclast-matrix interactions and their effect on osteoclastogenesis. For instance, fibrillar collagens have been shown to provide a co-stimulatory pathway for osteoclastogenesis through interaction with the osteoclast-associated receptor (OSCAR), a regulator of osteoclastogenesis expressed on the surface of pre-osteoclast cells. Based on this rationale, here we design two OSCAR-binding peptides and one recombinant OSCAR-binding protein, and we combine them with peptide-based hydrogels to study their effect on osteoclastogenesis. The OSCAR-binding peptides adopt the collagen triple-helical conformation and interact with OSCAR, as shown by circular dichroism spectropolarimetry and surface plasmon resonance. Furthermore, they have a positive effect on osteoclastogenesis, as demonstrated by appropriate gene expression and tartrate-resistant acid phosphatase staining typical of osteoclast formation. Combination of the OSCAR-binding peptides or the OSCAR-binding recombinant protein with peptide-based hydrogels enhances osteoclast differentiation when compared to the non-modified hydrogels, as demonstrated by multi-nucleation and by F-actin staining showing a characteristic osteoclast-like morphology. We envisage that these hydrogels could be used as a platform to study osteoclastogenesis and, in particular, to investigate the effect of costimulatory pathways involving OSCAR.
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影响因子：
3.9
作者：
Liao X;Bu Y;Zhang Y;Xu B;Liang J;Jia Q;Zhang C
通讯作者：
Zhang C
影响因子：
4.2
作者：
Lampiasi N;Russo R;Kireev I;Strelkova O;Zhironkina O;Zito F
通讯作者：
Zito F
影响因子：
2.5
作者：
Roscher A;Hasegawa T;Dohnke S;Ocaña-Morgner C;Amizuka N;Jessberger R;Garbe AI
通讯作者：
Garbe AI
影响因子：
5.4
作者：
Schultz, Heidi S.;Guo, Li;Panina, Svetlana
通讯作者：
Panina, Svetlana
影响因子：
14.8
作者：
Greenfield, Norma J.
通讯作者：
Greenfield, Norma J.