Shintani Nahoko, Hunziker Ernst B
ITI Research Institute for Dental and Skeletal Biology, University of Bern, Bern, Switzerland.
Arthritis Rheum. 2007 Jun;56(6):1869-79. doi: 10.1002/art.22701.
To compare the potential of bone morphogenetic proteins 2 and 7 (BMP-2 and BMP-7) and transforming growth factor beta1 (TGFbeta1) to effect the chondrogenic differentiation of synovial explants by analyzing the histologic, biochemical, and gene expression characteristics of the cartilaginous tissues formed.
Synovial explants derived from the metacarpal joints of calves were cultured in agarose. Initially, BMP-2 was used to evaluate the chondrogenic potential of the synovial explants under different culturing conditions. Under appropriate conditions, the chondrogenic effects of BMP-2, BMP-7, and TGFbeta1 were then compared. The differentiated tissue was characterized histologically, histomorphometrically, immunohistochemically, biochemically, and at the gene expression level.
BMP-2 induced the chondrogenic differentiation of synovial explants in a dose- and time-dependent manner under serum- and dexamethasone-free conditions. The expression levels of cartilage-related genes increased in a time-dependent manner. BMP-7 was more potent than BMP-2 in inducing chondrogenesis, but the properties of the differentiated tissue were similar in each case. The type of cartilaginous tissue formed under the influence of TGFbeta1 differed in terms of both cell phenotype and gene expression profiles.
The 3 tested members of the TGFbeta superfamily have different chondrogenic potentials and induce the formation of different types of cartilaginous tissue. To effect the full differentiation of synovial explants into a typically hyaline type of articular cartilage, further refinement of the stimulation conditions is required. This might be achieved by the simultaneous application of several growth factors.
通过分析所形成软骨组织的组织学、生化及基因表达特征,比较骨形态发生蛋白2和7(BMP - 2和BMP - 7)以及转化生长因子β1(TGFβ1)对滑膜外植体软骨形成分化的影响。
取自小牛掌指关节的滑膜外植体在琼脂糖中培养。最初,使用BMP - 2评估不同培养条件下滑膜外植体的软骨形成潜能。在合适条件下,随后比较BMP - 2、BMP - 7和TGFβ1的软骨形成作用。对分化组织进行组织学、组织形态计量学、免疫组织化学、生化及基因表达水平的特征分析。
在无血清和地塞米松条件下,BMP - 2以剂量和时间依赖性方式诱导滑膜外植体的软骨形成分化。软骨相关基因的表达水平随时间增加。BMP - 7在诱导软骨形成方面比BMP - 2更有效,但每种情况下分化组织的特性相似。在TGFβ1影响下形成的软骨组织类型在细胞表型和基因表达谱方面均有所不同。
TGFβ超家族的3个受试成员具有不同的软骨形成潜能,并诱导形成不同类型的软骨组织。为使滑膜外植体完全分化为典型的透明软骨类型,需要进一步优化刺激条件。这可能通过同时应用多种生长因子来实现。