Chen Jie, Zheng Rui, Zhang Peiling, Fan Hao, Jiang Hong, Zhou Guangdong
Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Dermatology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Sci Rep. 2025 May 14;15(1):16697. doi: 10.1038/s41598-025-01573-3.
Cartilage tissue engineering affords great promise for cartilage tissue regeneration in clinical practice. Unfortunately, in vitro engineered cartilage falls short of mechanical properties compared to natural cartilage, which has not yet become the mainstream of cartilage defect repair. Notably, the collagen fiber structure in the extracellular matrix (ECM) of chondrocytes accounts for the mechanical properties of engineered cartilage. Specifically, massive collagen fibers in ECM are covalently cross-linked by lysyl oxidase (LOX) to form a rigid cross-linked structure, contributing to certain mechanical properties. Accordingly, LOX may be a key enzyme for improving the mechanical properties of tissue-engineered cartilage in vitro. As reported, transforming growth factor-β1 (TGF-β1) can activate LOX via the SMAD-independent MAPK pathway, and β-aminopropionitrile (BAPN), an irreversible inhibitor of LOX, directly represses the cross-linking between macromolecules in the ECM of chondrocytes. In the present study, we intervened in cartilage regeneration in vitro using the aforementioned activator and inhibitor of LOX, thereby evaluating the quality and mechanical properties of tissue-engineered cartilage and further investigating the role of LOX in cartilage regeneration in vitro. Our results demonstrated that TGF-β1 improved the mechanical properties of cartilage in vitro at both two-dimensional and three-dimensional constructs by activating LOX. Therefore, further experimental studies are warranted to probe the activators of LOX and their mechanisms in cartilage regeneration in vitro.
软骨组织工程为临床实践中的软骨组织再生带来了巨大希望。不幸的是，与天然软骨相比，体外构建的工程化软骨在力学性能方面存在不足，这使其尚未成为软骨缺损修复的主流方法。值得注意的是，软骨细胞胞外基质（ECM）中的胶原纤维结构决定了工程化软骨的力学性能。具体而言，ECM中的大量胶原纤维通过赖氨酰氧化酶（LOX）共价交联形成刚性交联结构，从而赋予一定的力学性能。因此，LOX可能是体外改善组织工程化软骨力学性能的关键酶。据报道，转化生长因子-β1（TGF-β1）可通过不依赖SMAD的丝裂原活化蛋白激酶（MAPK）途径激活LOX，而β-氨基丙腈（BAPN）作为LOX的不可逆抑制剂，可直接抑制软骨细胞ECM中大分子之间的交联。在本研究中，我们使用上述LOX的激活剂和抑制剂干预体外软骨再生，从而评估组织工程化软骨的质量和力学性能，并进一步研究LOX在体外软骨再生中的作用。我们的结果表明，TGF-β1通过激活LOX在二维和三维构建物中均改善了体外软骨的力学性能。因此，有必要进行进一步的实验研究以探究LOX的激活剂及其在体外软骨再生中的机制。
