Duke J, Montufar-Solis D, Underwood S, Lalani Z, Hecht J T
Department of Orthodontics, Dental Branch, The University of Texas Health Science Center at Houston, TX, USA.
Apoptosis. 2003 Mar;8(2):191-7. doi: 10.1023/a:1022926811397.
Pseudoachondroplasia (PSACH) is a skeletal dysplasia caused by a mutation in cartilage oligomeric matrix protein (COMP), a glycoprotein of normal cartilage matrix. PSACH chondrocytes have a distinctive phenotype with enlarged rER cisternae containing COMP, aggrecan, type IX collagen, and chaperone proteins. Ultrastructural studies suggested that this accumulation compromises cell function, hastening cell death, and consequently reducing the number of cells in the growth plate contributing to linear bone growth. Using the alginate bead system, we cultured control and PSACH chondrocytes for twenty weeks and one year to determine the effect of the mutation on size and number of cartilage nodules; and the presence of apoptotic cell death (TUNEL assay). At 20 weeks, beads containing PSACH or control chondrocytes did not differ in size and number of cartilage nodules or number of TUNEL-positive cells. After one year, nodule number, size and percent cartilage per bead were significantly less in PSACH nodules, and the number of cells staining positive for apoptosis was significantly greater than in controls (71.8% vs. 44.6%). The increase in apoptosis in PSACH nodules correlates with a decrease in growth of cartilage, supporting our hypothesis that death of damaged cells contributes to the growth plate defects in PSACH.
假性软骨发育不全（PSACH）是一种骨骼发育不良，由软骨寡聚基质蛋白（COMP）突变引起，COMP是正常软骨基质的一种糖蛋白。PSACH软骨细胞具有独特的表型，其粗面内质网池扩大，含有COMP、聚集蛋白聚糖、IX型胶原蛋白和伴侣蛋白。超微结构研究表明，这种积累损害细胞功能，加速细胞死亡，从而减少生长板中对线性骨生长有贡献的细胞数量。我们使用藻酸盐珠系统，将对照软骨细胞和PSACH软骨细胞培养20周和1年，以确定突变对软骨结节大小和数量的影响，以及凋亡细胞死亡的存在情况（TUNEL检测）。在20周时，含有PSACH或对照软骨细胞的珠子在软骨结节大小和数量或TUNEL阳性细胞数量上没有差异。1年后，PSACH结节中的结节数量、大小和每颗珠子的软骨百分比显著减少，凋亡染色阳性的细胞数量显著多于对照组（71.8%对44.6%）。PSACH结节中凋亡的增加与软骨生长的减少相关，支持了我们的假设，即受损细胞的死亡导致了PSACH中的生长板缺陷。
