Alterations in the Sensing and Transport of Phosphate and Calcium by Differentiating Chondrocytes*
Alterations in the Sensing and Transport of Phosphate and Calcium by Differentiating Chondrocytes*
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分化软骨细胞改变磷酸盐和钙的传感和运输*
DOI：
10.1074/jbc.m007757200
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
J. Henderson
中科院分区：
文献类型：
--
作者：
Dashen Wang;L. Canaff;D. Davidson;Adrijana Corluka;Hanlong Liu;G. Hendy;J. Henderson
在软骨内骨形成和骨折愈合期间，致力于软骨形成的细胞经历了一段时间受限的分化程序，其特征是其表型和基因表达的顺序变化。这导致了软骨模板的制造、重塑和矿化，骨在其上铺设。关节软骨细胞经历类似的但受限的分化程序，不会进行矿化，除非是在病理条件下，如骨关节炎。软骨发育和代谢障碍的发病机制，包括骨软骨发育不良、骨折不愈合和骨关节炎，目前仍不清楚。我们使用CFK2模型来研究磷酸盐和钙离子在调节软骨形成和软骨成熟的通路中的潜在作用。使用已经在体内和体外表征的形态、生化和分子标记的组合，在4周内监测分化情况。CFK2细胞表达III型钠依赖的磷酸转运体Glvr-1和Ram-1，以及钙敏感机制。细胞外磷酸盐和甲状旁腺激素相关蛋白对Glvr-1表达和活性的调节仅限于CFK2分化的早期阶段，II型胶原、蛋白多糖和IHH的表达证明了这一点。另一方面，细胞外钙对钙敏感受体的表达和活性的调控在分化2周后最为明显，伴随着X型胶原表达、碱性磷酸酶活性和甲状旁腺激素/甲状旁腺激素相关蛋白受体表达的增加。根据这些对磷酸盐和钙的感知和运输的时间受限的变化，我们预测细胞外的磷酸盐在软骨细胞的分化过程中发挥作用，而细胞外的钙在其分化过程的后期发挥作用。
During endochondral bone formation and fracture healing, cells committed to chondrogenesis undergo a temporally restricted program of differentiation that is characterized by sequential changes in their phenotype and gene expression. This results in the manufacture, remodeling, and mineralization of a cartilage template on which bone is laid down. Articular chondrocytes undergo a similar but restricted differentiation program that does not proceed to mineralization, except in pathologic conditions such as osteoarthritis. The pathogenesis of disorders of cartilage development and metabolism, including osteochondrodysplasia, fracture non-union, and osteoarthritis remain poorly defined. We used the CFK2 model to examine the potential roles of phosphate and calcium ions in the regulatory pathways that mediate chondrogenesis and cartilage maturation. Differentiation was monitored over a 4-week period using a combination of morphological, biochemical, and molecular markers that have been characterized in vivo and in vitro. CFK2 cells expressed the type III sodium-dependent phosphate transporters Glvr-1 and Ram-1, as well as a calcium-sensing mechanism. Regulated expression and activity of Glvr-1 by extracellular phosphate and parathyroid hormone-related protein was restricted to an early stage of CFK2 differentiation, as evidenced by expression of type II collagen, proteoglycan, and Ihh. On the other hand, regulated expression and activity of a calcium-sensing receptor by extracellular calcium was most evident after 2 weeks of differentiation, concomitant with an increase in type X collagen expression, alkaline phosphatase activity and parathyroid hormone/parathyroid hormone-related protein receptor expression. On the basis of these temporally restricted changes in the sensing and transport of phosphate and calcium, we predict that extracellular phosphate plays a role in the commitment of chondrogenic cells to differentiation, whereas extracellular calcium plays a role at a later stage in their differentiation program.
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DOI：
10.1016/s0021-9258(18)33299-x
发表时间：
1983-01
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Ellis E. GolubS;Susan C. Schattschneider;Peter Berthold;A.G. Burke;Irving;Shapiro
通讯作者：
Ellis E. GolubS;Susan C. Schattschneider;Peter Berthold;A.G. Burke;Irving;Shapiro
影响因子：
15.9
作者：
Bikle, DD;Ratnam, A;Pillai, S
通讯作者：
Pillai, S
影响因子：
10.5
作者：
KARAPLIS, AC;LUZ, A;MULLIGAN, RC
通讯作者：
MULLIGAN, RC
克隆大鼠甲状旁腺细胞系表达甲状旁腺激素相关肽，但不表达甲状旁腺激素本身。
DOI：
10.1016/0006-291x(89)91969-4
发表时间：
1989
影响因子：
3.1
作者：
Ikeda,K;Weir,EC;Sakaguchi,K;Burtis,WJ;Zimering,M;Mangin,M;Dreyer,BE;Brandi,ML;Aurbach,GD;Broadus,AE
通讯作者：
Broadus,AE
影响因子：
19.6
作者：
Kavanaugh, MP;Kabat, D
通讯作者：
Kabat, D