Kim Woo-Jin, Bae Jieun, Lee Eun-Hye, Kim Jaehyung, Kim Pil-Jong, Ma Peter X, Woo Kyung Mi
Department of Molecular Genetics, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, 08826, Republic of Korea.
Biomedical Knowledge Engineering Laboratory, Dental Research Institute, Seoul National University, Seoul, 08826, Republic of Korea.
Mater Today Bio. 2024 Aug 8;28:101182. doi: 10.1016/j.mtbio.2024.101182. eCollection 2024 Oct.
Prosthesis-induced pathological calcification is a significant challenge in biomaterial applications and is often associated with various reconstructive medical procedures. It is uncertain whether the fibrous extracellular matrix (ECM) adjacent to biomaterials directly triggers osteogenic trans-differentiation in nearby cells. To investigate this possibility, we engineered a heterogeneous polystyrene fibrous matrix (PSF) designed to mimic the ECM. Our findings revealed that the myoblasts grown on this PSF acquired osteogenic properties, resulting in mineralization both and . Transcriptomic analyses indicated a notable upregulation in the expression of the long noncoding RNA metastsis-associated lung adenocarcinoma transcript 1 () in the C2C12 myoblasts cultured on PSF. Intriguingly, silencing curtailed the PSF-induced mineralization and downregulated the expression of bone morphogenetic proteins () and osteogenic markers. Further, we found that PSF prompted the activation of Yap1 signaling and epigenetic modifications in the promoter, crucial for the expression of . These results indicate that the fibrous matrix adjacent to biomaterials can instigate upregulation, subsequently driving osteogenic trans-differentiation in myoblasts and ectopic calcification through its transcriptional regulation of osteogenic genes, including . Our findings point to a novel therapeutic avenue for mitigating prosthesis-induced pathological calcification, heralding new possibilities in the field of biomaterial-based therapies.
假体诱导的病理性钙化是生物材料应用中的一项重大挑战，并且常常与各种重建医疗程序相关联。与生物材料相邻的纤维状细胞外基质（ECM）是否直接触发附近细胞的成骨转分化尚不确定。为了研究这种可能性，我们设计了一种旨在模拟ECM的异质聚苯乙烯纤维基质（PSF）。我们的研究结果表明，在这种PSF上生长的成肌细胞获得了成骨特性，导致[具体部位1]和[具体部位2]均发生矿化。转录组分析表明，在PSF上培养的C2C12成肌细胞中，长链非编码RNA转移相关肺腺癌转录本1（[具体名称1]）的表达显著上调。有趣的是，沉默[具体名称1]可减少PSF诱导的矿化，并下调骨形态发生蛋白（[具体名称2]）和成骨标志物的表达。此外，我们发现PSF促使Yap1信号通路激活以及[具体名称1]启动子的表观遗传修饰，这对于[具体名称1]的表达至关重要。这些结果表明，与生物材料相邻的纤维基质可促使[具体名称1]上调，随后通过其对包括[具体名称2]在内的成骨基因的转录调控，驱动成肌细胞的成骨转分化和异位钙化。我们的研究结果指出了一条减轻假体诱导的病理性钙化的新治疗途径，为基于生物材料的治疗领域带来了新的可能性。
