Cellular interactions regulate stem cell differentiation in tri-culture.
Cellular interactions regulate stem cell differentiation in tri-culture.
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DOI：
10.1080/03008207.2016.1230106
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发表时间：
2016-11
影响因子：
2.9
通讯作者：
Lu HH
中科院分区：
文献类型：
--
作者：
Wang IE;Bogdanowicz DR;Mitroo S;Shan J;Kala S;Lu HH
目前，控制软组织-骨界面再生的机制，如前交叉韧带（ACL）和骨之间的过渡，尚不清楚。聚焦于acl -骨插入，本研究验证了韧带细胞（成纤维细胞）和骨细胞（成骨细胞）之间的相互作用启动界面再生的新假设。具体来说，这些异型细胞相互作用指导界面相关细胞群的成纤维软骨分化，这里定义为韧带成纤维细胞和骨髓基质细胞（BMSC）。本研究的目的是研究异型细胞相互作用对骨髓间充质干细胞或成纤维细胞生长和生物合成的影响，以及在三培养中纤维软骨相关标志物的表达。还确定了成纤维细胞和成骨细胞之间的细胞间物理接触和旁分泌相互作用的影响。我们发现，在成纤维细胞和成骨细胞的三培养中，BMSC比韧带成纤维细胞表现出更大的成纤维软骨潜能。BMSC的生长减慢，蛋白多糖的产生和TGF-β3的表达增加。此外，三培养通过旁分泌因子调节BMSC应答，有趣的是，成纤维细胞与成骨细胞的接触进一步促进了蛋白聚糖和TGF-β1的合成，诱导了BMSC中SOX9的表达。总的来说，本研究的结果表明，成纤维细胞与成骨细胞的相互作用在调节纤维软骨再生的干细胞生态位中起着重要作用，这些相互作用的机制是由旁分泌因子指导的，并通过细胞与细胞的直接接触而增强。
Currently, the mechanism governing the regeneration of the soft tissue-to-bone interface, such as the transition between the anterior cruciate ligament (ACL) and bone, is not known. Focusing on the ACL-to-bone insertion, this study tests the novel hypothesis that interactions between cells from the ligament (fibroblasts) and bone (osteoblasts) initiate interface regeneration. Specifically, these heterotypic cell interactions direct the fibrochondrogenic differentiation of interface-relevant cell populations, defined here as ligament fibroblasts and bone marrow stromal cells (BMSC). The objective of this study is to examine the effects of heterotypic cellular interactions on BMSC or fibroblast growth and biosynthesis, as well as expression of fibrocartilage-relevant markers in tri-culture. The effects of cell-cell physical contact and paracrine interactions between fibroblasts and osteoblasts were also determined. It was found that, in tri-culture with fibroblasts and osteoblasts, BMSC exhibited greater fibrochondrogenic potential than ligament fibroblasts. The growth of BMSC decreased while proteoglycan production and TGF-β3 expression increased. Moreover, tri-culture regulated BMSC response via paracrine factors, and interestingly, fibroblast-osteoblast contact further promoted proteoglycan and TGF-β1 synthesis and induced SOX9 expression in BMSC. Collectively, the findings of this study suggest that fibroblast-osteoblast interactions play an important role in regulating the stem cell niche for fibrocartilage regeneration, and the mechanisms of these interactions are directed by paracrine factors and augmented with direct cell-cell contact.