Hunter G K, Bader S M
Department of Pathology, Mount Sinai Hospital, Toronto, Ontario, Canada.
J Theor Biol. 1989 May 22;138(2):195-211. doi: 10.1016/s0022-5193(89)80139-0.
Recent studies in this laboratory have suggested that proteoglycan may function as a Ca ion-exchanger in the calcification of epiphyseal growth plate cartilage. Specifically, it has been proposed that phosphate liberated from hypertrophic chondrocytes may displace calcium ions bound to the anionic groups of proteoglycans, thereby raising the Ca x PO4 activity product above the threshold for precipitation of hydroxyapatite. In order to determine whether this mechanism is quantitatively feasible, a mathematical model of the interaction between Ca, Na, proteoglycan and phosphate has now been developed. This model is based on a general binding theory, and utilizes previously-determined values for the binding constants of the Ca-proteoglycan interaction, inhibition constants for the effect of Na and phosphate on this interaction, and literature values for the concentrations of proteoglycan, Na and Ca in epiphyseal cartilage. Using this approach, it was predicted that the free Ca concentration in epiphyseal cartilage in the absence of phosphate will be 1.55 mM. At 0.7 mM phosphate, the approximate concentration in non-calcified cartilage matrix, the free Ca concentration will be 2.40 mM, corresponding to a Ca x PO4 product of 1.68 (mM)2. In order to achieve a Ca x PO4 product sufficient for spontaneous precipitation of hydroxyapatite [approximately 4.3 (mM)2], a phosphate concentration of approximately 1.40 mM is required. Therefore, calcification of epiphyseal cartilage matrix by the mechanism described above will require an approximate doubling of the phosphate concentration in the pre-calcifying zones, indicating that the release of a fraction of the intracellular phosphate could trigger the calcification process.
本实验室最近的研究表明，蛋白聚糖可能在骨骺生长板软骨钙化过程中充当钙离子交换剂。具体而言，有人提出，从肥大软骨细胞释放的磷酸盐可能会取代与蛋白聚糖阴离子基团结合的钙离子，从而使钙与磷酸根的活性乘积升高至羟基磷灰石沉淀阈值以上。为了确定该机制在数量上是否可行，现已建立了一个钙、钠、蛋白聚糖和磷酸盐相互作用的数学模型。该模型基于一般结合理论，并利用先前确定的钙与蛋白聚糖相互作用的结合常数、钠和磷酸盐对该相互作用影响的抑制常数，以及骨骺软骨中蛋白聚糖、钠和钙浓度的文献值。采用这种方法预测，在无磷酸盐的情况下，骨骺软骨中的游离钙浓度将为1.55 mM。在0.7 mM磷酸盐（非钙化软骨基质中的近似浓度）时，游离钙浓度将为2.40 mM，对应的钙与磷酸根乘积为1.68（mM）²。为了达到足以使羟基磷灰石自发沉淀的钙与磷酸根乘积[约4.3（mM）²]，需要约1.40 mM的磷酸盐浓度。因此，通过上述机制使骨骺软骨基质钙化将需要预钙化区的磷酸盐浓度大约翻倍，这表明细胞内一部分磷酸盐的释放可能会触发钙化过程。
