The sites of the lesions were tibia (2 cases), femur (1 case), and rib (1 case). The forms of FD were monostotic in one case and polyostotic in three cases. Radiologically, plain films and computed tomography (CT) showed osteolytic lesions with poorly delineated margins within and/or near areas having a ground-glass appearance. In the osteolytic lesions, simple cystic changes associated with old FD could be excluded by enhanced magnetic resonance imaging (MRI). Histopathologically, two cases were osteosarcoma, one case was malignant fibrous histiocytoma (MFH), and one case was fibrosarcoma. The management of this disease should be decided according to the type of primary high-grade bone sarcoma. One patient, with MFH, was dead of lung metastasis 13 months after surgery. The others are alive without disease.

We have previously reported that transforming growth factor b (TGF-b) plays an essential role in receptor activator of nuclear factorkB ligand (RANKL)-induced osteoclastogenesis. However, the detailed underlying molecular mechanisms still remain unclear. Formaldehyde-assisted isolation of regulatory elements (FAIRE) and chromatin immunoprecipitation (ChIP) followed by sequencing (FAIRE-seq and ChIP-seq) analyses indicated the cooperation of Smad2/3 with c-Fos during osteoclastogenesis. Biochemical analysis and immunocytochemical analysis revealed that physical interaction between Smad2/3 and c-Fos is required for their nuclear translocation. The gene expression of nuclear factor of activated T-cells, cytoplasmic 1 (Nfatc1), a key regulator of osteoclastogenesis, was regulated by RANKL and TGF-b, and c-Fos binding to open chromatin sites was suppressed by inhibition of TGF-b signaling by SB431542. Conversely, Smad2/3 binding to Nfatc1 was impaired by c-Fos deficiency. These results suggest that TGF-b regulates RANKL-induced osteoclastogenesis through reciprocal cooperation between Smad2/3 and c-Fos.

Bone turnover is finely tuned by cells in the bone milieu, including osteoblasts, osteoclasts, and osteocytes. Osteoclasts are multinucleated giant cells with a bone-resorbing function that play a critical role in regulating skeletal homeostasis. Osteoclast differentiation is characterized by dramatic changes in morphology and gene expression following receptor activator of nuclear factor-kappa-Β ligand (RANKL) stimulation. We performed single-cell RNA-sequencing analyses of human and murine osteoclast-lineage cells (OLCs) and found that OLCs in the mitotic phase do not differentiate into mature osteoclasts. We also identified a guanosine triphosphatase (GTPase) family member, RAB38, as a highly expressed molecule in both human and murine osteoclast clusters; RAB38 gene expression is associated with dynamic changes in histone modification and transcriptional regulation. Silencing Rab38 expression by using short hairpin RNA (shRNA) inhibited osteoclast differentiation and maturation. In summary, we established an integrated fate map of human and murine osteoclastogenesis; this will help identify therapeutic targets in bone diseases.

The overall incidence of orthopedic surgeries in patients with RA significantly decreased, accompanied by improved clinical outcomes because of the expanded use of effective drugs; however, the declining trend differed between procedures or locations. The results from the present study suggest that there might be a change in supply and demand for orthopedic surgeries.