Shankar G, Davison I, Helfrich M H, Mason W T, Horton M A
ICRF Haemopoiesis Research Group, St. Bartholomew's Hospital, London, UK.
J Cell Sci. 1993 May;105 ( Pt 1):61-8. doi: 10.1242/jcs.105.1.61.
Cell-matrix interactions have been shown to play an important role in regulating cell function and behaviour. In bone, where calcified matrix formation and resorption events are required to be in dynamic equilibrium, regulation of adhesive interactions between bone cells and their matrix is critical. The present study focuses on the osteoclast, the bone resorbing cell, as well as integrins, which are cell surface adhesion receptors that mediate osteoclast attachment to bone matrix. In osteoclasts, the most abundant integrin receptor is the vitronectin receptor (VNR, alpha v beta 3). The objective of the study was to investigate changes in intracellular calcium, a regulator of osteoclast function, following addition of peptides that bind integrins, in particular the alpha v beta 3 form of the vitronectin receptor (VNR), which is highly expressed in osteoclasts. The study demonstrated a unique spatial localisation of the calcium signal in response to cell membrane receptor occupancy by integrin ligands in rat osteoclasts. Addition of peptides with the Arg-Gly-Asp (RGD) sequence such as BSP-IIA, GRGDSP and GRGDS to rat osteoclasts evoked an immediate increase in free calcium ion concentration [Ca2+]i, localised to the nuclei and to the thin cytoplasmic skirt. These responses were inhibited by F11, a monoclonal antibody to the rat integrin beta 3 chain, as well as echistatin, a snake venom shown to colocalise with the alpha v chain in osteoclasts, suggesting that the calcium signal is mediated by the alpha v beta 3 form of VNR.(ABSTRACT TRUNCATED AT 250 WORDS)
细胞与基质的相互作用已被证明在调节细胞功能和行为中发挥重要作用。在骨骼中，钙化基质的形成和吸收过程需要处于动态平衡，因此调节骨细胞与其基质之间的黏附相互作用至关重要。本研究聚焦于破骨细胞，即负责骨吸收的细胞，以及整合素，整合素是介导破骨细胞与骨基质附着的细胞表面黏附受体。在破骨细胞中，最丰富的整合素受体是玻连蛋白受体（VNR，αvβ3）。该研究的目的是在添加能结合整合素的肽段后，研究破骨细胞功能调节因子细胞内钙的变化，特别是在破骨细胞中高表达的玻连蛋白受体（VNR）的αvβ3形式。该研究证明了在大鼠破骨细胞中，钙信号对整合素配体占据细胞膜受体的反应具有独特的空间定位。向大鼠破骨细胞添加具有精氨酸 - 甘氨酸 - 天冬氨酸（RGD）序列的肽段，如BSP-IIA、GRGDSP和GRGDS，会引发游离钙离子浓度[Ca2+]i立即升高，且定位在细胞核和薄的细胞质裙边。这些反应被大鼠整合素β3链的单克隆抗体F11以及在破骨细胞中显示与αv链共定位的蛇毒echistatin抑制，这表明钙信号由VNR的αvβ3形式介导。（摘要截断于250字）
