Carcinoma/pathology* ; Giant Cells/pathology* ; Humans ; Osteoclasts/pathology* ; Pancreas/pathology* ; Pancreatic Neoplasms/surgery*

Cellular immune responses as well as generalized and periarticular bone loss are the key pathogenic features of rheumatoid arthritis (RA). Under the pathological conditions of RA, dysregulated inflammation and immune processes tightly interact with skeletal system, resulting in pathological bone damage via inhibition of bone formation or induction of bone resorption. Single-cell omics technologies are revolutionary tools in the field of modern biological research.They enable the display of the state and function of cells in various environments from a single-cell resolution, thus making it conducive to identify the dysregulated molecular mechanisms of bone destruction in RA as well as the discovery of potential therapeutic targets and biomarkers. Here, we summarize the latest findings of single-cell omics technologies in osteoimmunology research in RA. These results suggest that single-cell omics have made significant contributions to transcriptomics and dynamics of specific cells involved in bone remodeling, providing a new direction for our understanding of cellular heterogeneity in the study of osteoimmunology in RA.
Humans ; Osteoclasts/physiology* ; Arthritis, Rheumatoid/pathology* ; Inflammation/pathology* ; Bone and Bones/pathology* ; Bone Resorption/pathology*

Multiple myeloma (MM) is a B cell malignancy characterized by enhanced bone loss that commonly associated with diffuse osteopenia, focal lytic lesions, pathologic fractures, and bone pain. The key mechanism of bone damage in myeloma is the abnormal regulation in bone metastasis, with increased osteoclast function and decreased osteoblast activity. This article reviewed the factors implicated, such as receptor activator of nuclear factor-kappaB (RANK), receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), macrophage inflammatory protein-1alpha (MIP-1alpha), SDF-1 and Wnt pathway. Further understanding of the regulation system of bone homeostasis helps to offer possible targets for future therapy.
Bone Diseases ; etiology ; Bone and Bones ; pathology ; Humans ; Multiple Myeloma ; complications ; pathology ; Osteoblasts ; pathology ; Osteoclasts ; pathology

Osteoclast-like giant cell tumor of the pancreas is a very rare tumor. Despite their striking morphologic resemblance to certain mesenchymal tumors of bone and tendon sheath, it has been suggested that these tumors may arise from epithelial precursors. This unusual tumor presents in the 6th or 7th decade with a nearly equal gender ratio. Pure forms of osteoclast-like giant cell tumor have a better prognosis because they have a predilection to local spread, are slower to metastasize and rarely metastasize to lymph nodes, but these forms are very rare. We present an osteoclast-like giant cell tumor arising in the body of the pancreas in a 71 year-old male patient. The tumor was composed of two major cell types: atypical mononuclear cells and abundant osteoclast-like multinucleated giant cells. Immunohistochemical studies showed that atypical cells were strongly reactive for vimentin and focally reactive for cytokeratin. In contrast, the giant cells were immunoreactive for CD68, but negative for cytokeratin. Three months later, the tumor size increased and liver metastasis was newly developed. He died at 11 months after the diagnosis.
Aged ; Giant Cell Tumors/*pathology ; Humans ; Male ; Osteoclasts/*pathology ; Pancreatic Neoplasms/*pathology

Gorham-Stout disease (GSD) is a sporadic chronic disease characterized by progressive bone dissolution, absorption, and disappearance along with lymphatic vessel infiltration in bone-marrow cavities. Although the osteolytic mechanism of GSD has been widely studied, the cause of lymphatic hyperplasia in GSD is rarely investigated. In this study, by comparing the RNA expression profile of osteoclasts (OCs) with that of OC precursors (OCPs) by RNA sequencing, we identified a new factor, semaphorin 3A (Sema3A), which is an osteoprotective factor involved in the lymphatic expansion of GSD. Compared to OCPs, OCs enhanced the growth, migration, and tube formation of lymphatic endothelial cells (LECs), in which the expression of Sema3A is low compared to that in OCPs. In the presence of recombinant Sema3A, the growth, migration, and tube formation of LECs were inhibited, further confirming the inhibitory effect of Sema3A on LECs in vitro. Using an LEC-induced GSD mouse model, the effect of Sema3A was examined by injecting lentivirus-expressing Sema3A into the tibiae in vivo. We found that the overexpression of Sema3A in tibiae suppressed the expansion of LECs and alleviated bone loss, whereas the injection of lentivirus expressing Sema3A short hairpin RNA (shRNA) into the tibiae caused GSD-like phenotypes. Histological staining further demonstrated that OCs decreased and osteocalcin increased after Sema3A lentiviral treatment, compared with the control. Based on the above results, we propose that reduced Sema3A in OCs is one of the mechanisms contributing to the pathogeneses of GSD and that expressing Sema3A represents a new approach for the treatment of GSD.
Animals ; Mice ; Endothelial Cells/metabolism* ; Lymphatic Vessels ; Osteoclasts/pathology* ; Osteolysis, Essential/pathology* ; Semaphorin-3A/metabolism*

OBJECTIVETo detect the expression of RANKL and OPG protein in the giant cell lesions of jaw and to study the mechanism of this lesion.

METHODSRANKL and OPG were detected by immunohistochemistry (SP) in 24 paraffin-embedded and 2 frozen specimens of central giant cell lesion of jaw.

RESULTSRANKL signals were strongly positive in the vascular epithelial cells. They also could be found in fibrous stroma, bone matrix, and stromal spindle cells, even in some cytomembrane of multinucleated giant cells. OPG was detected in multinucleated giant cells and a fraction of round mononuclear cells.

CONCLUSIONSActive vascular epithelial cells are contributed to the formation of multinucleated giant cells through regulating RANKL, and RANKL could play its role by paracrine and autocrine, which might be inhibited by OPG.

Giant Cells ; metabolism ; pathology ; Humans ; Jaw Diseases ; metabolism ; pathology ; Osteoclasts ; metabolism ; Osteoprotegerin ; metabolism ; RANK Ligand ; metabolism

Gastric carcinoma with osteoclast-like giant cells (OGCs) is an extremely rare tumor. So far, only six cases have been reported in the literature. Here we report an additional case of this tumor in a Chinese 78-year-old man presented with abdominal pain, vomiting, and hematemesis. Physical examination and gastroscopy revealed a tumor in the gastric antrum. The biopsy and pathological findings indicated a gastric adenocarcinoma with OGCs, which were present in both the tumor and the metastatic lymph nodes. Further immunohistochemical staining indicated that OGCs were reactive with CD68, CD45, and vimentin protein, but not with pancytokeratin, carcinoembryonic antigen, or epithelial membrane antigen, suggesting the monocytic/histiocytic derivation of these OGCs. In situ hybridization for Epstein-Barr virus showed no nuclear positivity in either adenocarcinoma or OGCs. Postoperative follow-up showed that the patient had survived for at least 6 months without recurrence. Further investigation is warranted to clearly define the prognostic significance of OGCs in gastric carcinoma.
Aged ; Giant Cells ; metabolism ; pathology ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Male ; Osteoclasts ; metabolism ; pathology ; Stomach Neoplasms ; genetics ; metabolism ; pathology

OBJECTIVE: To observe the morphology of eroded auditory ossicles obtained in middle ear surgery for cholesteatoma and to investigate the mechanism of bone erosion in cholesteatoma. METHOD: The morphology of eroded auditory ossicles in 8 cholesteatoma cases and 2 normal cases were observed with light microscopy. The ultrastructure of eroded auditory ossicles in 5 cholesteatoma cases and the ultrastructure of control bones in external ear canal of 2 cases were observed and compared with transmission electron microscopy. RESULT: Osteomyelitis and multinucleate osteoclasts with ruffled borders were observed in the eroded auditory ossicles of cholesteatoma. Intramembranous and endochondral ossification were both observed. The obvious bone destruction and remodeling were observed consistently. CONCLUSION Osteoclasts and Osteomyelitis are both responsible for bone destruction in cholesteatoma. Intramembranous and endochondral ossification may co-participate in bone remodeling. Osteogenesis is also a basic pathologic phenomena in cholesteatoma. The obvious bone destruction and remodeling can coexist in cholesteatoma cases.
Case-Control Studies ; Cholesteatoma, Middle Ear ; pathology ; Ear Ossicles ; pathology ; ultrastructure ; Humans ; Microscopy, Electron, Transmission ; Osteoclasts ; pathology ; ultrastructure

Biopsy, Fine-Needle ; Carcinoma ; pathology ; Endosonography ; Giant Cells ; pathology ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Osteoclasts ; pathology ; Pancreas ; diagnostic imaging ; pathology ; Pancreatic Neoplasms ; pathology

Undifferentiated carcinoma with osteoclast-like giant cells is a rare neoplasm of exocrine pancreas. Till recently, some cases have been reported, however histogenesis of the tumors are controversial and their characteristic findings have not been described yet. Thirty five-year-old men and 75-year-old men were presented with upper abdominal pain and a palpable mass. On computed tomography, one case showed a well enhancing solid tumor with low density and the other was showed a mainly cystic tumor with peripheral enhancement in the body and tail of the pancreas. One case accompanied multiple metastatic liver masses with subhepatic lymph node enlargement. Tumor staining was seen on angiography. Biopsy and pancreatectomy were performed. Pathological findings revealed tumors composed of neoplastic spindle shaped or pleomorphic large cells with scattered non-neoplastic osteoclast-like giant cells. In one case, there were small foci of adenocarcinoma components in the periphery of the tumor. On immunohistochemical stain, neoplastic cells showed focal positivity for epithelial membrane antigen and vimentin. Tumors were diagnosed as undifferented carcinoma with osteoclast-like giant cells. We report these rare cases with a review of literature.
Adult ; Aged ; Carcinoma/*pathology/radiography/surgery ; Giant Cells/*pathology ; Humans ; Male ; Osteoclasts/*pathology ; Pancreatic Neoplasms/*pathology/radiography/surgery ; Tomography, X-Ray Computed