Rumours, Lies Coupled With Erlotinib

Osteoclasts are multinucleated bone-resorbing cells formed by fusion of mononuclear cells derived from the monocyte/macrophage lineage [osteoclast precursors (OCPs)]. OCPs exist in the peripheral circulation or within the bone marrow (Kindle et?al. 2006). They undergo extravasation and migration under the osteoblasts to reach the surface of bone matrix (Brandi & Collin-Osdoby 2006). After OCPs differentiate into tartrate-resistant acid phosphatase-positive mononuclear cells (TRAP+ pre-OCs), these cells differentiate into multinucleated osteoclasts by cell fusion in the presence of receptor activator of NF-kappaB ligand (RANKL), which is mainly provided by the osteoblasts (Nakahama 2010). In this process, pre-OC should distinguish cell fusion partner with other type of cells. Integrin, a large family of heterodimeric cell surface receptors, has pivotal effects on the interactions of cells with other cells or with the extracellular matrix (Springer 1990). Integrins are noncovalently linked ���� heterodimers. Four �� subunits and ��2 subunits were expressed on monocytes/macrophages (Smith 2008). Among them, CD11b/18 integrin pair (macrophage antigen 1, Mac-1) was expressed on pre-OC and reported to play an important role in the osteoclastogenesis by our previous study (Hayashi et?al. 2008). Mac-1 binds to a wide range of ligands, including the blood coagulation protein fibrinogen (Wright et?al. 1988), intercellular adhesion molecule-1 and -2 (ICAM-1 and -2) (Diamond et?al. 1990), and the complement protein iC3b (Beller et?al. 1982). Among them, the possible candidates of counter receptors against Mac-1 are ICAM-1 and ICAM-2, which are expressed on pre-OCs (Diacovo et?al. 1994; Xie et?al. 1995; Fagerholm et?al. 2006). This study examined the possible role of intercellular adhesion molecules in osteoclastogenesis using primary cultured bone marrow macrophages (BMMs). It is reported here that ICAM-2, expressed on OCPs, may play an important role in osteoclastogenesis induced by RANKL or tumor necrosis factor �� (TNF��) through the interaction with Mac-1. Adhesion molecules expressed on bone marrow cells were tested. Flow cytometric analysis of bone marrow cells showed CD11b positive cells occupied 60% of the whole population. 15% of CD11b positive cells also expressed both ICAM-1 and ICAM-2. 30% of the bone marrow cells were positive for both ICAM-1 and ICAM-2, but negative for CD11b (Fig.?1A�CC and Fig. S1 in Supporting Information). Quantitative reverse transcription�Cpolymerase chain reaction (real-time PCR) experiment showed that mRNA expression levels of adhesion molecules on bone marrow cells were ICAM-1?