骨骼发育中的转录因子Cbfa1

骨骼由骨和软骨共同构成 .最近的研究表明 ,转录因子Cbfa1不仅控制骨的形成和生长 ,还影响软骨组织成熟 ,并且可能与破骨细胞分化和软骨血管侵入有关 .

A Simplified Method for Purifying Osteoclasts from Human Giant Cell Tumor of Bone

Objective: To purify and identify the osteoclasts from the tissue of humangiant cell tumor of bone. Methods: We have developed a new method that allows the purification oflarge numbers of authentic osteoclasts (OCs). The OCs were isolated from tissue of human giant celltumor of bone by 0.25% trypsin and collagenase. We characterized OCs in terms of the expression ofdifferent phenotypic markers of OCs. The phenotypic markers of OC included Tartrate-resistant acidphosphatase staining (TRAP). The expression of calcitonin receptor (CTR), cathepsin K and receptoractivator of necrosis factor κB (RANK) mRNA were examined by RT-PCR. Results: The OC cell purifiedby above method functioned normally in vitro. The purity was about 79.7%. They showed the normalosteoclast phenotypes markers of OC. Conclusion: The method provides a system for performingbiochemical and molecular studies of OCs. The study indicates that the method of purifying theosteoclasts from human GCT cell can be used for research of bone metabolism.

Osteoclast-like giant cell tumors of the pancreas and liver

Osteoclast-like giant cell tumors （OGCT） are rare abdominal tumors, which mainly occur in the pancreas. The neoplasms are composed of two distinct cell populations and frequently show an inhomogenous appearance with cystic structures. However, due to the rarity of these tumors, only very limited clinical data are available. Imaging features and sonographic appearance have hardly been characterized. Here we report on two cases of osteoclast-like giant cell tumors, one located within the pancreas, the other within the liver, in which OGCTs are extremely rare. Both patients were investigated by contrast sonography, which demonstrated a complex, partly cystic and strongly vascularized tumor within the head of the pancreas in the first patient and a large, hypervascularized neoplasm with calcifications within the liver in the second patient. The liver OGCT responded well to a combination of carboplatin, etoposide and paclitaxel. With a combination of surgical resection, radiofrequency ablation and chemotherapy, the patient＇s survival is currently more than 15 too, making him the longest survivor with an OGCT of the liver to date.

Possible effect of fluid shear stress on osteoclastogenesis

Bone remodeling is performed under the joint action of osteoblasts and osteoclasts. Since the effect of osteoclasts has been gradually recognized on bone and joint diseases, targeted researches toward osteoclasts have become a hot research field. This article reviews the relevant medical literature concerning the possible effects of the fluid shear stress (FSS) on the osteoclastogenesis chiefly from the aspects of RANKL-RANK-OPG system, the macrophage colony-stimulating factor (M-CSF), and calcitonin receptor (CTR). On the basis of the changes of the expression of osteoclastic activities, it is suggested that FSS is a potent, important regulator of bone metabolism.

Effect of osteoprotegerin in combination with interleukin-6 on inhibition of osteoclast differentiation

Objective： To observe the effect of recombinant interleukin-6 （IL-6） and osteoprotegerin （OPG） on inhibiting bone absorption induced by receptor activa- tor for nuclear factor- rB ligand （RANKL） in murine osteo- clast precursor cells （OCPs） model. Methods： RAW 264.7 cells were solely treated with 50 ng/ml RANKL for 1 day, and then they were divided into three groups： RANKL （control group）, RANKL＋IL-6 （IL-6 group） and RANKL＋IL-6＋OPG （combination group）. These cells were harvested and investigated by means of HE stain- ing under light microscope after consecutive 9 days. Furthermore, staining tartrate-resistant acid phosphatase （TRAP）-positive multinucleated cells were detected by in- verted phase contrast microscope. The absorption pits of bone slices were observed under scanning electron microscope. Results： The number of mature osteoclast cells in control group was more than that in IL-6 alone or IL-6 com- bined with OPG group （P〈0.05）. Interestingly, this experi- ment has also demonstrated that there was a large number of TRAP-positive multinucleated osteoclasts （more than 3 nuclei） and several bone absorption formation in the con- trol group, whereas the outcome was completely different in both IL-6 group and IL-6＋OPG group （P〈0.05）. Conclusion： IL-6 can suppress the differentiation of mature osteoclasts as directly adding it into the RAW 264.7 cells induced by 50 ng/ml RANKL, and further the effect of osteolysis is remarkably reduced. When treatment with IL- 6 combined with OPG, a more effective strategy for the treat- ment of osteoporosis is reached.

Gastric carcinoma with osteoclast-like giant cells:a case report and review of the literature

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-Burr 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.

Nanostructure and mechanical properties of the osteocyte lacunar-canalicular network-associated bone matrix revealed by quantitative nanomechanical mapping

Osteocytes are the main bone cells embedded in the bone matrix where they form a large surface-area network called the lacunar-canalicular network （LCN）, interconnecting their resident spaces with the lacunae by the canaliculi. Increasing evidence points toward osteocytes playing a pivotal role in maintaining bone quality. On the one hand, osteocytes transmit mechanical strain and microenvironmental signals through the LCN to regulate the activity of osteoblasts and osteoclasts; on the other hand, osteocytes are suggested to be able to remodel the LCN-associated bone matrix. However, due to the challenges involved in the assessment and characterization of the LCN-associated bone matrix, little is known about its structure and the corresponding mechanical properties. In this work, we used quantitative nanomechanical mapping, backscattered electron imaging, and nanoindentation to characterize the LCN-associated bone matrix. The results show that the techniques can be used to probe the LCN-associated bone matrix. Nanoindentation and quantitative mechanical mapping reveal spatially inhomogeneous mechanical properties of the bone matrix associated with the osteocyte lacunae and canaliculi. The obtained nano-topography and corresponding nano-mechanical maps reveal altered mechanical properties in the immediate vicinity of the osteocyte lacunae and canaliculi, which cannot be explained solely by the topographic change.

Breaking the vicious cycle between tumor cell proliferation and bone resorption by chloroquine-loaded and bone-targeted polydopamine nanoparticles

The vicious cycle between tumor cell proliferation and bone resorption remarkably elevates the progression and metastasis of bone tumors.Here,we fabricated polyethylene glycol-conjugated alendronate-functionalized and chloroquine(CQ)-loaded polydopamine nanoparticles(PPA/CQ)for efficient treatment of bone tumors via breaking the vicious cycle.The nanoparticles were efficiently accumulated to the bone tissues,especially the osteolytic lesions around tumors.CQ released from PPA/CQ inhibited osteoclastogenesis via preventing the degradation of tumor necrosis factor(TNF)receptor-associated receptor 3 to attenuate the osteolysis in bone tumors.On the other hand,CQ blocked the autophagy in cancer cells,resulting in improved photothermal killing of cancer cells.Finally,the in vivo experiment revealed that PPA/CQ-associated treatment efficiently inhibited both tumor growth and osteolysis.This work suggests that autophagy inhibition-associated photothermal therapy could be a promising strategy for treating malignant bone tumors.

Effect of the same mechanical loading on osteogenesis and osteoclastogenesis in vitro

Purpose： To investigate the influence of the same mechanical loading on osteogenesis and osteoclastogenesis in vitro. Methods： Primary osteoblasts, bone marrow-derived mesenchymal stem cells （BMSCs, cultured in osteoinductive medium） and RAW264.7 cells cultured in osteoclast inductive medium were all subjected to a 1000μstrain （μs） at 1 Hz cyclic mechanical stretch for 30 min （twice a day）. Results： After mechanical stimulation, the alkaline phosphatase （ALP） activity, osteocalcin protein level of the osteoblasts and BMSCs were all enhanced, and the mRNA levels of ALP and collagen type I increased. Additionally, extracellular-deposited calcium of both osteoblasts and BMSCs increased. At the same time, the activity of secreted tartrate-resistant acid phosphatase, the number of tartrate-resistant acid phosphatase-positive multinucleated cells, matrix metalloproteinase-9 protein levels of RAW264.7 cells and the extracellular calcium solvency all decreased. Conclusion： The results demonstrated that 1000 μs cyclic mechanical loading enhanced osteoblasts activity, promoted osteoblastic differentiation of BMSCs and restrained osteoclastogenesis of RAW264.7 cells in vitro.