在幼兒時期，骨骼的生長取決于靠近身體所有長骨（long bone）末端的生長板（growth plate）。這些生長板由軟骨細(xì)胞組成，后者產(chǎn)生一種支持新骨組織形成的支架，而它們本身是由軟骨祖細(xì)胞的干細(xì)胞樣細(xì)胞產(chǎn)生的。為了讓長骨正常生長，軟骨細(xì)胞必須在整個生長期內(nèi)不斷產(chǎn)生。此前，研究人員普遍認(rèn)為個體在胚胎發(fā)育期間形成有限數(shù)量的干細(xì)胞，隨后用于骨骼生長，直到它們耗盡人體才停止生長。近日，一項新的研究對此觀點提出了挑戰(zhàn)，相關(guān)研究結(jié)果發(fā)表在國際頂級期刊Nature上。
在這項新的研究中，來自瑞典卡羅林斯卡學(xué)院等機(jī)構(gòu)的研究人員發(fā)現(xiàn)小鼠的骨骼生長與血液、皮膚等其他組織產(chǎn)生新細(xì)胞的原理是一樣的，存在于骨骼中的干細(xì)胞數(shù)量并不會逐漸消耗殆盡。他們發(fā)現(xiàn)，在小鼠胚胎發(fā)育過程中，一小群細(xì)胞克隆由相同的祖細(xì)胞產(chǎn)生，而在小鼠出生后，這些細(xì)胞形成了較大的穩(wěn)定的克隆，經(jīng)證實這是軟骨祖細(xì)胞獲得再生能力的結(jié)果。這種祖細(xì)胞行為是不斷產(chǎn)生新細(xì)胞和組織的典型表現(xiàn)，與已知的皮膚、血液和腸道組織的更新生長類似。早前人們已發(fā)現(xiàn)這些組織中存在祖細(xì)胞并位于一種非常特殊的微環(huán)境，即干細(xì)胞壁龕（stem cell niche）中，這種干細(xì)胞壁龕不僅產(chǎn)生必需的組織細(xì)胞，如皮膚細(xì)胞和血細(xì)胞，也能夠讓這些祖細(xì)胞完成自我更新。這項新的研究首次證實在小鼠體內(nèi)的生長板中也存在干細(xì)胞壁龕，當(dāng)這種局部的干細(xì)胞微環(huán)境受到破壞，骨骼生長就會停止，為人們理解骨骼生長提供了新的證據(jù)。
研究人員Andrei Chagin指出，骨骼生長新機(jī)制的發(fā)現(xiàn)也將幫助解釋以前令人不解的現(xiàn)象，比如在發(fā)生某些基團(tuán)突變的患者中觀察到的骨骼無限制生長。同時，如果這項新發(fā)現(xiàn)也適用于人類，那么將為治療生長障礙兒童提供新的思路。
推薦閱讀原文：
A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plate.
Longitudinal bone growth in children is sustained by growth plates, narrow discs of cartilage that provide a continuous supply of chondrocytes for endochondral ossification. However, it remains unknown how this supply is maintained throughout childhood growth. Chondroprogenitors in the resting zone are thought to be gradually consumed as they supply cells for longitudinal growth, but this model has never been proved. Here, using clonal genetic tracing with multicolour reporters and functional perturbations, we demonstrate that longitudinal growth during the fetal and neonatal periods involves depletion of chondroprogenitors, whereas later in life, coinciding with the formation of the secondary ossification centre, chondroprogenitors acquire the capacity for self-renewal, resulting in the formation of large, stable monoclonal columns of chondrocytes. Simultaneously, chondroprogenitors begin to express stem cell markers and undergo symmetric cell division. Regulation of the pool of self-renewing progenitors involves the hedgehog and mammalian target of rapamycin complex 1 (mTORC1) signalling pathways. Our findings indicate that a stem cell niche develops postnatally in the epiphyseal growth plate, which provides a continuous supply of chondrocytes over a prolonged period.
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