Osteoporosis is a major health problem; however, the mechanisms regulating adult bone mass are poorly understood. Cas-interacting zinc finger protein (CIZ) is a nucleocytoplasmic shuttling protein that localizes at cell adhesion plaques that form where osteoblasts attach to substrate. To investigate the potential role of CIZ in regulating adult bone mass, we examined the bones in CIZ-deficient mice. Bone volume was increased and the rates of bone formation were increased in CIZ-deficient mice, whereas bone resorption was not altered. CIZ deficiency enhanced the levels of mRNA expression of genes encoding proteins related to osteoblastic phenotypes, such as alkaline phosphatase (ALP) as well as osterix mRNA expression in whole long bones. Bone marrow cells obtained from the femora of CIZ-deficient mice revealed higher ALP activity in culture and formed more mineralized nodules than wild-type cells. CIZ deficiency enhanced bone morphogenetic protein (BMP)–induced osteoblastic differentiation in bone marrow cells in cultures, indicating that BMP is the target of CIZ action. CIZ deficiency increased newly formed bone mass after femoral bone marrow ablation in vivo. Finally, BMP-2–induced bone formation on adult mouse calvariae in vivo was enhanced by CIZ deficiency. These results establish that CIZ suppresses the levels of adult bone mass through inhibition of BMP-induced activation of osteoblasts.

The endoplasmic reticulum (ER) stress transducer BBF2H7/CREB3L2 is an ER-resident transmembrane transcription factor. In response to physiological ER stress, it is processed at the transmembrane region to generate a cytoplasmic N terminus, which contains a basic leucine zipper (bZIP) domain, and luminal C terminus. The BBF2H7 N terminus functions as a transcription factor to promote the expression of ER-Golgi trafficking-related genes and plays crucial roles in chondrocyte differentiation. Here, we found that the BBF2H7 C terminus is secreted into the extracellular space as a signaling molecule for cell-to-cell communication. The secreted BBF2H7 C terminus directly binds to both Indian hedgehog and its receptor Patched-1, followed by activation of Hedgehog signaling, resulting in promoting the proliferation of neighboring chondrocytes. The dual N- and C-terminal functions of BBF2H7 triggered by physiological ER stress may allow chondrocytes to simultaneously regulate distinct cellular events for differentiation and proliferation in developing cartilage.

Background: BBF2H7 promotes cartilage matrix protein secretion through activation of Sec23a expression during chondrogenesis.Results: Sox9 induces BBF2H7 expression, followed by accelerating secretion of cartilage matrix proteins in chondrocytes.Conclusion: Sox9 simultaneously induces Bbf2h7 and Col2, followed by promoting secretion of Col2 through activation of BBF2H7-Sec23a signaling.Significance: This might be the first to define mechanisms for cartilage matrix protein secretion regulated by Sox9.

There are several methods for evaluating stability of the joint during total knee replacement (TKR). Activities of daily living demand mechanical loading to the knee joint, not only in full extension, but also in mid-flexion. The purpose of this study was to compare the varus-valgus stability throughout flexion in knees treated with either cruciate-retaining or posterior-stabilised TKR, using an intra-operative navigation technique. A total of 34 knees underwent TKR with computer navigation, during which the investigator applied a maximum varus-valgus stress to the knee while steadily moving the leg from full extension to flexion both before and after prosthetic implantation. The femorotibial angle was measured simultaneously by the navigation system at every 10° throughout the range of movement. It was found that posterior-stabilised knees had more varus-valgus laxity than cruciate-retaining knees at all angles examined, and the differences were statistically significant at 10° (p = 0.0093), 20° (p = 0.0098) and 30° of flexion (p = 0.0252).

The combination of nevus of Ota and meningeal melanocytoma has been reported in only four cases in the literature, including the current case. This is the first case coinciding with intracerebral hemorrhage, suggesting the necessity for careful follow-up with radiological images.