OPN is produced by osteoblasts [109], [110] and [111], as well as osteoclasts [110], [112] and [113], and is considered to play important roles in bone formation, resorption, and remodeling [109], [110], [111], [112], [113], [114], [115] and [116]. It was found previously that OPN

can promote the attachment selleck inhibitor of osteoclasts possibly via interaction with the RGDS amino acid sequence of OPN and αvβ3 integrin of osteoclasts [107]. We investigated the spatial gene expression of OPN mRNA in periodontal ligaments and in the interradicular septum (IRS) of alveolar bone during physiological tooth movement in rats [117]. OPN mRNA was detected in osteoclasts and only in osteocytes located adjacently in the resorption site of the interradicular septum, strongly suggesting that OPN participates in bone resorption. The experimental model for orthodontic tooth movement developed by Waldo and Rothblatt provides further information [28]. Initially, the positive signals were buy ZD1839 expressed only in cells

located close to the compressed bone surface of the IRS. After 2 days of treatment, the expression area spread until almost all of the osteocytes of the IRS were positive for OPN expression. This suggests a signaling mechanism caused by mechanical stress that is dispersed to surrounding cells, moving from only those at the distal side (compressed area) to include those cells at the mesial side (tensioned area of IRS). Following this event, numerous osteoclasts were recruited to the bone surface within the entire IRS. The appearance of osteoclasts occurred with a short delay to the increase in the proportion of OPN mRNA-positive 2-hydroxyphytanoyl-CoA lyase osteocytes.

However, this increase in the number of OPN mRNA-expressing osteocytes in the IRS was temporary. An in vitro migration assay demonstrated the chemotactic effect of OPN toward osteoclastic cells, and results of an in vivo blocking assay using an RGDS peptide further confirmed this chemotactic role of OPN to stimulate the migration of osteoclasts to bone surface. The bone surface of the osteoclast anchoring site is enriched in OPN [116]. CCN2 is a matricellular protein belonging to the CCN family of secretory proteins that contain 38 conserved cysteine residues [67]. “CCN” is an acronym for Connective tissue growth factor (CTGF), Cysteine-rich protein (Cyr61), and Nephroblastoma overexpressed gene. There are six members of the CCN family, namely CCN1 to CCN6: cyr61/cef10, ctgf/fisp12, nov, elm1/wisp-1, rcop-1/wisp-2, and wisp-3. CCN2, otherwise known as CTGF, is a ubiquitous 38-KD protein originally isolated from the culture supernatant of human umbilical cord venous vascular endothelial cells [118]. CCN2 proteins have four distinct modules: insulin-like growth factor binding protein module, Von Willebrand factor module, thrombospondin-homology module and C-terminal cysteine knot module (CT module).