Effect of a retinoic acid analogue on BMP-driven pluripotent stem cell chondrogenesis.
Effect of a retinoic acid analogue on BMP-driven pluripotent stem cell chondrogenesis.
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DOI：
10.1038/s41598-024-52362-3
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发表时间：
2024-02-01
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
骨关节炎是最常见的退行性关节疾病，会导致关节软骨(AC)退化、慢性疼痛和不能动弹。缺乏提供组织修复的适当疗法，再加上关节置换植入物的有限寿命，表明需要替代的AC再生策略。将人类多能干细胞(HPSCs)分化为AC祖细胞可能会提供一种长期的再生解决方案，但由于仍然依赖生长因子来概括发育信号过程，因此仍然有限。最近，维甲酸受体(RARs)的小分子激活剂TTNPB被证明足以指导hPSCs的中胚层分化和早期软骨形成。在这里，我们修改了以前的分化方案，在细胞中补充TTNPB并在特定的时间给予BMP2以促进早期发育(称为快速E方案)。转录分析表明，RAR信号的激活在方案的早期阶段显着上调了与肢体和胚胎骨骼发育相关的基因，并在后期上调了与AC发育相关的基因。从快速-E获得的软骨前体细胞可以产生软骨球，表达AC相关的基质蛋白，如润滑素、聚集素和II型胶原，但另外还表达X型胶原，这表明细胞肥大。该方案可以为骨关节炎的细胞治疗策略奠定基础，并提高对人类AC发展的理解。
Osteoarthritis is the most common degenerative joint condition, leading to articular cartilage (AC) degradation, chronic pain and immobility. The lack of appropriate therapies that provide tissue restoration combined with the limited lifespan of joint-replacement implants indicate the need for alternative AC regeneration strategies. Differentiation of human pluripotent stem cells (hPSCs) into AC progenitors may provide a long-term regenerative solution but is still limited due to the continued reliance upon growth factors to recapitulate developmental signalling processes. Recently, TTNPB, a small molecule activator of retinoic acid receptors (RARs), has been shown to be sufficient to guide mesodermal specification and early chondrogenesis of hPSCs. Here, we modified our previous differentiation protocol, by supplementing cells with TTNPB and administering BMP2 at specific times to enhance early development (referred to as the RAPID-E protocol). Transcriptomic analyses indicated that activation of RAR signalling significantly upregulated genes related to limb and embryonic skeletal development in the early stages of the protocol and upregulated genes related to AC development in later stages. Chondroprogenitors obtained from RAPID-E could generate cartilaginous pellets that expressed AC-related matrix proteins such as Lubricin, Aggrecan, and Collagen II, but additionally expressed Collagen X, indicative of hypertrophy. This protocol could lay the foundations for cell therapy strategies for osteoarthritis and improve the understanding of AC development in humans.
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影响因子：
--
作者：
Fernández-Lloris, R;Viñals, F;Ventura, F
通讯作者：
Ventura, F
影响因子：
4
作者：
Cho, SH;Oh, CD;Chun, JS
通讯作者：
Chun, JS
DOI：
10.1073/pnas.0511294103
发表时间：
2006-03-07
影响因子：
11.1
作者：
Jacobs, S;Lie, DC;Evans, RM
通讯作者：
Evans, RM
影响因子：
2.7
作者：
Chapman, DL;Agulnik, I;Papaioannou, VE
通讯作者：
Papaioannou, VE
影响因子：
4.6
作者：
Goedhart J;Luijsterburg MS
通讯作者：
Luijsterburg MS