Momberger T S, Levick J R, Mason R M
Division of Biomedical Sciences, Faculty of Medicine, Imperial College London, SW7 2AZ, United Kingdom.
Matrix Biol. 2005 Dec;24(8):510-9. doi: 10.1016/j.matbio.2005.08.006. Epub 2005 Oct 14.
Hyaluronan (HA) is an essential component of synovial interstitial matrix and synovial fluid, but the link between its production and joint use is unclear. HA secretion is enhanced by joint distension in vivo, but direct proof that synoviocytes exhibit mechanosensitive HA secretion is lacking. We tested this in vitro. Primary rabbit synoviocyte (PRS) cultures from microdissected synovial intima were subjected to 180 min of maintained 10% static stretch, or to 10 min of 10% static stretch followed by 170 min relaxation, in a Flexcell 2000 apparatus. Stretch stimulated HA secretion into the medium over 3 h by 57%. Notably, a short stretch (10 min) was as effective as sustained stretch. Actinomycin D and cycloheximide abolished stretch-stimulated HA secretion and also reduced basal HA secretion rate. RT-PCR showed that HAS2 was the major hyaluronan synthase expressed, but there was no increase in HAS2 mRNA (or other isoforms) in continuously stretched cells, and only a small increase (20%) at 180 min in cells stretched for the first 10-30 min. However HAS2 transcription increased 10-fold in response to TGF-beta1 and IL-1beta. Thus HA secretion by intimal synoviocytes is regulated by a mechanosensitive pathway which depends on transcription and de novo protein synthesis, possibly of HAS2, but also of other proteins involved in HA secretion.
透明质酸（HA）是滑膜间质基质和滑液的重要组成部分，但其产生与关节使用之间的联系尚不清楚。体内关节扩张可增强HA分泌，但滑膜细胞表现出机械敏感的HA分泌的直接证据尚缺乏。我们在体外对此进行了测试。在Flexcell 2000仪器中，将来自显微解剖滑膜内膜的原代兔滑膜细胞（PRS）培养物进行180分钟的10%静态拉伸，或进行10分钟的10%静态拉伸，随后170分钟松弛。拉伸在3小时内刺激HA分泌到培养基中的量增加了57%。值得注意的是，短时间拉伸（10分钟）与持续拉伸一样有效。放线菌素D和环己酰亚胺消除了拉伸刺激的HA分泌，也降低了基础HA分泌率。逆转录聚合酶链反应（RT-PCR）显示HAS2是主要表达的透明质酸合酶，但在持续拉伸的细胞中HAS2 mRNA（或其他异构体）没有增加，在最初拉伸10 - 30分钟的细胞中，180分钟时仅略有增加（20%）。然而，HAS2转录在转化生长因子-β1（TGF-β1）和白细胞介素-1β（IL-1β）作用下增加了10倍。因此，内膜滑膜细胞的HA分泌受一种机械敏感途径调节，该途径依赖于转录和从头蛋白质合成，可能涉及HAS2，也可能涉及其他参与HA分泌的蛋白质。
