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新型软骨诱导肽TP8显著促进新软骨修复，且不激活骨形成。

TP8, A Novel Chondroinductive Peptide, Significantly Promoted Neo-Cartilage Repair without Activating Bone Formation.

作者信息

Zhu Mingjing, Jiang Siqing, Li Xingyang, Zhong Wenchao, Cao Wei, Luo Qianting, Wu Antong, Wu Gang, Zhang Qingbin

机构信息

Department of Temporomandibular Joint, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction & Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, 510180, China.

Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, 1081 LA, the Netherlands.

出版信息

Adv Healthc Mater. 2025 Mar;14(6):e2401752. doi: 10.1002/adhm.202401752. Epub 2024 Dec 17.

DOI:10.1002/adhm.202401752
PMID:39690790
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11874676/
Abstract

The repair of large cartilage defects remains highly challenging in the fields of orthopedics and oral and maxillofacial surgery. A chondroinductive agent is promising to activate endogenous mesenchymal stem cells (MSCs) so as to facilitate cartilage regeneration. In this study, we analyze the crystallographic data of the critical binding domain of transforming growth factor β3 (TGF-β3) with its type II receptor and successfully develop a novel chondroinductive peptide - TGF-β3-derived peptide No. 8 (TP8) that can induce an ectopic cartilage formation without obvious bone formation. TP8 shows a comparable capacity as TGF-β3 in enhancing glycosaminoglycans (GAGs) and proteoglycans (PGs) secretion in the micromass of bone marrow MSCs (BMSCs) and promoting the expression of chondrogenic markers in comparison with the Control group. TP8 induces a significantly higher expression of the SRY-box transcription factor 9 (Sox9) gene than TGF-β3. Moreover, TP8 significantly upregulates the phosphorylation of Smad1/5 but not MAPK/JNK or Smad 2/3. The knockdown of low-density lipoprotein receptor (LDLR) -related protein-1 (Lrp1), a transmembrane endocytosis receptor, nullifies the TP8-induced Sox9 expression. In the critical-size cartilage defects in rabbit medial femoral condyles, TP8 can induce neo-cartilage formation with a significantly thicker deep zone in comparison with the TGF-β3 and Control. These findings suggest a promising application potential of TP8 in cartilage tissue engineering.

摘要

在骨科以及口腔颌面外科领域，大型软骨缺损的修复仍然极具挑战性。一种软骨诱导剂有望激活内源性间充质干细胞（MSCs），从而促进软骨再生。在本研究中，我们分析了转化生长因子β3（TGF-β3）与其II型受体的关键结合域的晶体学数据，并成功开发出一种新型软骨诱导肽——TGF-β3衍生肽8号（TP8），它能够诱导异位软骨形成而无明显骨形成。与对照组相比，TP8在增强骨髓间充质干细胞（BMSCs）微团中糖胺聚糖（GAGs）和蛋白聚糖（PGs）分泌以及促进软骨生成标志物表达方面显示出与TGF-β3相当的能力。TP8诱导SRY盒转录因子9（Sox9）基因的表达显著高于TGF-β3。此外，TP8显著上调Smad1/5的磷酸化水平，但不影响MAPK/JNK或Smad 2/3。低密度脂蛋白受体（LDLR）相关蛋白1（Lrp1）是一种跨膜内吞受体，敲低其表达可消除TP8诱导的Sox9表达。在兔股骨内侧髁的临界尺寸软骨缺损中，与TGF-β3和对照组相比，TP8可诱导新软骨形成，其深部区域明显更厚。这些发现表明TP8在软骨组织工程中具有广阔的应用潜力。

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