Calreticulin inhibits inflammation-induced osteoclastogenesis and bone resorption.

Osteoclasts play key roles in bone remodeling and pathologic osteolytic disorders such as inflammation, infection, bone implant loosening, rheumatoid arthritis, metastatic bone cancers, and pathological fractures. Osteoclasts are formed by the fusion of monocytes in response to receptor activators of NF-κB-ligand (RANKL) and macrophage colony stimulating factor 1 (M-CSF). Calreticulin (CRT), a commonly known intracellular protein as a calcium-binding chaperone, has an unexpectedly robust anti-osteoclastogenic effect when its recombinant form is applied to osteoclast precursors in vitro or at the site of bone inflammation externally in vivo.

Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential.

The stem cells that maintain and repair the postnatal skeleton remain undefined. One model suggests that perisinusoidal mesenchymal stem cells (MSCs) give rise to osteoblasts, chondrocytes, marrow stromal cells, and adipocytes, although the existence of these cells has not been proven through fate-mapping experiments. We demonstrate here that expression of the bone morphogenetic protein (BMP) antagonist gremlin 1 defines a population of osteochondroreticular (OCR) stem cells in the bone marrow.

CA-074Me compound inhibits osteoclastogenesis via suppression of the NFATc1 and c-FOS signaling pathways.

The osteoclast is an integral cell of bone resorption. Since osteolytic disorders hinge on the function and dysfunction of the osteoclast, understanding osteoclast biology is fundamental to designing new therapies that curb osteolytic disorders. The identification and study of lysosomal proteases, such as cathepsins, have shed light on mechanisms of bone resorption.

Aggravation of inflammatory response by costimulation with titanium particles and mechanical perturbations in osteoblast- and macrophage-like cells.

The interface between bone tissue and metal implants undergoes various types of mechanical loading, such as strain, compression, fluid pressure, and shear stress, from daily activities. Such mechanical perturbations create suboptimal environments at the host bone-implant junction, causing an accumulation of wear particles and debilitating osseous integration, potentially leading to implant failure. While many studies have focused on the effect of particles on macrophages or osteoprogenitor cells, differential and combined effects of mechanical perturbations and particles on such cell types have not been extensively studied.

Modern interpretation of giant cell tumor of bone: predominantly osteoclastogenic stromal tumor.

Owing to striking features of numerous multinucleated cells and bone destruction, giant cell tumor (GCT) of bone, often called as osteoclastoma, has drawn major attractions from orthopaedic surgeons, pathologists, and radiologists. The name GCT or osteoclastoma gives a false impression of a tumor comprising of proliferating osteoclasts or osteoclast precursors. The underlying mechanisms for excessive osteoclastogenesis are intriguing and GCT has served as an exciting disease model representing a paradigm of osteoclastogenesis for bone biologists.

New application of optical agent to image angiogenesis in hindlimb ischemia.

Optical agents targeting α(v)β₃ are potential tools to image the angiogenic response to limb ischemia. The left (L) femoral artery was ligated in 17 mice and sham surgery performed on the contralateral right (R) hindlimb. Seven days later, IntegriSense (2 nmol) was injected into 11 mice and 6 were probe controls.

Actin and ERK1/2-CEBPβ signaling mediates phagocytosis-induced innate immune response of osteoprogenitor cells.

Wear particles at the host bone-implant interface are a major challenge for successful bone implant arthoplasties. Current understanding of aseptic loosening consists of macrophage-mediated inflammatory responses and increasing osteoclastogenesis, which lead to an imbalance between bone formation and resorption. Despite its significant role in bone regeneration and implant osteointegration, the osteoprogenitor response to wear particles has been examined recent years.

Nuclear presence of nuclear factor of activated T cells (NFAT) c3 and c4 is required for Toll-like receptor-activated innate inflammatory response of monocytes/macrophages.

Nuclear factor of activated T cells (NFATs) are crucial transcription factors that tightly control proinflammatory cytokine expression for adaptive immunity in T and B lymphocytes. However, little is known about the role of NFATs for innate immunity in macrophages. In this study, we report that NFAT is required for Toll-like receptor (TLR)-initiated innate immune responses in bone marrow-derived macrophages (BMMs).