Thouverey C, Bechkoff G, Pikula S, Buchet R
Department of Biochemistry, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
Osteoarthritis Cartilage. 2009 Jan;17(1):64-72. doi: 10.1016/j.joca.2008.05.020. Epub 2008 Jul 7.
Pathological mineralization is induced by unbalance between pro- and anti-mineralization factors. In calcifying osteoarthritic joints, articular chondrocytes undergo terminal differentiation similar to that in growth plate cartilage and release matrix vesicles (MVs) responsible for hydroxyapatite (HA) or calcium pyrophosphate dihydrate (CPPD) deposition. Inorganic pyrophosphate (PP(i)) is a likely source of inorganic phosphate (P(i)) to sustain HA formation when hydrolyzed but also a potent inhibitor preventing apatite mineral deposition and growth. Moreover, an excess of PP(i) can lead to CPPD formation, a marker of pathological calcification in osteoarthritic joints. It was suggested that the P(i)/PP(i) ratio during biomineralization is a turning point between physiological and pathological mineralization. The aim of this work was to determine the conditions favoring either HA or CPPD formation initiated by MVs.
MVs were isolated from 17-day-old chicken embryo growth plate cartilages and subjected to mineralization in the presence of various P(i)/PP(i) ratios. The mineralization kinetics and the chemical composition of minerals were determined, respectively, by light scattering and infrared spectroscopy.
The formation of HA is optimal when the P(i)/PP(i) molar ratio is above 140, but is completely inhibited when the ratio decreases below 70. The retardation of any mineral formation is maximal at P(i)/PP(i) ratio around 30. CPPD is exclusively produced by MVs when the ratio is below 6, but it is inhibited for the ratio exceeding 25.
Our findings are consistent with the P(i)/PP(i) ratio being a determinant factor leading to pathological mineralization or its inhibition.
病理性矿化是由促矿化因子和抗矿化因子之间的失衡引起的。在钙化性骨关节炎关节中，关节软骨细胞经历类似于生长板软骨的终末分化，并释放负责羟基磷灰石（HA）或二水焦磷酸钙（CPPD）沉积的基质小泡（MVs）。无机焦磷酸（PP(i)）在水解时可能是维持HA形成的无机磷酸盐（P(i)）来源，但也是阻止磷灰石矿物沉积和生长的有效抑制剂。此外，过量的PP(i)可导致CPPD形成，这是骨关节炎关节病理性钙化的标志物。有人提出生物矿化过程中的P(i)/PP(i)比值是生理矿化和病理矿化之间的转折点。这项工作的目的是确定有利于MVs引发HA或CPPD形成的条件。
从17日龄鸡胚生长板软骨中分离出MVs，并在存在各种P(i)/PP(i)比值的情况下进行矿化。分别通过光散射和红外光谱法测定矿化动力学和矿物质的化学成分。
当P(i)/PP(i)摩尔比高于140时，HA的形成最佳，但当该比值降至70以下时则完全受到抑制。在P(i)/PP(i)比值约为30时，任何矿物质形成的延迟最大。当比值低于6时，CPPD仅由MVs产生，但当比值超过25时则受到抑制。
我们的研究结果与P(i)/PP(i)比值是导致病理性矿化或其抑制的决定因素这一观点一致。
