基于光氧化还原比成像的成熟和退变依赖性关节软骨代谢。
Maturation- and degeneration-dependent articular cartilage metabolism via optical redox ratio imaging.
机构信息
Comparative Biomedical Sciences Program, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Department of Mechanical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA.
出版信息
J Orthop Res. 2022 Aug;40(8):1735-1743. doi: 10.1002/jor.25214. Epub 2021 Nov 18.
From the two metabolic processes in healthy cartilage, glycolysis has been associated with proliferation and oxidative phosphorylation (oxphos) with matrix synthesis. Recently, metabolic dysregulation was significantly correlated with cartilage degradation and osteoarthritis progression. While these findings suggest maturation predisposes cartilage to metabolic instability with consequences for tissue maintenance, these links have not been shown. Therefore, this study sought to address three hypotheses (a) chondrocytes exhibit differential metabolic activity between immaturity (0-4 months), adolescence (5-18 months), and maturity (>18 months); (b) perturbation of metabolic activity has consequences on expression of genes pertinent to cartilage tissue maintenance; and (c) severity of cartilage damage is positively correlated with glycolysis and oxphos activity as well as optical redox ratio in postadolescent cartilage. Porcine femoral cartilage samples from pigs (3 days to 6 years) underwent optical redox ratio imaging, which measures autofluorescence of NAD(P)H and FAD. Gene expression analysis and histological scoring was conducted for comparison against imaging metrics. NAD(P)H and FAD autofluorescence both demonstrated increasing intensity with age, while optical redox ratio was lowest in adolescent samples compared to immature or mature samples. Inhibition of glycolysis suppressed expression of Col2, Col1, ADAMTS4, and ADAMTS5, while oxphos inhibition had no effect. FAD fluorescence and optical redox ratio were positively correlated with histological degeneration. This study demonstrates maturation- and degeneration-dependent metabolic activity in cartilage and explores the consequences of this differential activity on gene expression. This study aids our basic understanding of cartilage biology and highlights opportunity for potential diagnostic applications.
从健康软骨中的两种代谢过程来看,糖酵解与增殖有关,而氧化磷酸化(oxphos)则与基质合成有关。最近,代谢失调与软骨降解和骨关节炎进展显著相关。虽然这些发现表明成熟会使软骨代谢不稳定,从而影响组织维持,但这些联系尚未得到证实。因此,本研究试图解决三个假设:(a)软骨细胞在不成熟(0-4 个月)、青春期(5-18 个月)和成熟(>18 个月)之间表现出不同的代谢活性;(b)代谢活性的改变会对与软骨组织维持相关的基因表达产生影响;(c)青春期后软骨的损伤严重程度与糖酵解和 oxphos 活性以及氧化还原光学比呈正相关。来自猪(3 天至 6 岁)的股骨软骨样本进行了氧化还原光学比成像,该成像测量 NAD(P)H 和 FAD 的自发荧光。进行基因表达分析和组织学评分以与成像指标进行比较。NAD(P)H 和 FAD 自发荧光均随年龄增长而增强,而与不成熟或成熟样本相比,青春期样本的氧化还原光学比最低。糖酵解抑制会抑制 Col2、Col1、ADAMTS4 和 ADAMTS5 的表达,而 oxphos 抑制则没有影响。FAD 荧光和氧化还原光学比与组织退变呈正相关。本研究证明了软骨中的成熟和退变依赖性代谢活性,并探讨了这种差异活性对基因表达的影响。本研究有助于我们对软骨生物学的基本理解,并强调了潜在诊断应用的机会。