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Bone Research

Minhao Gao, Weiyang Gao, J M Papadimitriou, Changqing Zhang, Junjie Gao, Minghao Zheng
Exosomes are a heterogeneous group of cell-derived membranous structures, which mediate crosstalk interaction between cells. Recent studies have revealed a close relationship between exosomes and bone homeostasis. It is suggested that bone cells can spontaneously secret exosomes containing proteins, lipids and nucleic acids, which then to regulate osteoclastogenesis and osteogenesis. However, the network of regulatory activities of exosomes in bone homeostasis as well as their therapeutic potential in bone injury remain largely unknown...
2018: Bone Research
Xu Cao
No abstract text is available yet for this article.
2018: Bone Research
Xiao Chen, Xin Zhi, Jun Wang, Jiacan Su
RANKL signaling is essential for osteoclastogenesis. Its role in osteoblastic differentiation and bone formation is unknown. Here we demonstrate that RANK is expressed at an early stage of bone marrow mesenchymal stem cells (BMSCs) during osteogenic differentiation in both mice and human and decreased rapidly. RANKL signaling inhibits osteogenesis by promoting β-catenin degradation and inhibiting its synthesis. In contrast, RANKL signaling has no significant effects on adipogenesis of BMSCs. Interestingly, conditional knockout of rank in BMSCs with Prx1 -Cre mice leads to a higher bone mass and increased trabecular bone formation independent of osteoclasts...
2018: Bone Research
Ruoshi Xu, Sanjoy Kumar Khan, Taifeng Zhou, Bo Gao, Yaxing Zhou, Xuedong Zhou, Yingzi Yang
How osteoblast cells are induced is a central question for understanding skeletal formation. Abnormal osteoblast differentiation leads to a broad range of devastating craniofacial diseases. Here we have investigated intramembranous ossification during cranial bone development in mouse models of skeletal genetic diseases that exhibit craniofacial bone defects. The GNAS gene encodes Gαs that transduces GPCR signaling. GNAS activation or loss-of-function mutations in humans cause fibrous dysplasia (FD) or progressive osseous heteroplasia (POH) that shows craniofacial hyperostosis or craniosynostosis, respectively...
2018: Bone Research
Ling Ye, Feng Lou, Fanyuan Yu, Demao Zhang, Chenglin Wang, Fanzi Wu, Xin Li, Yilin Ping, Xiao Yang, Jing Yang, Dian Chen, Bo Gao, Dingming Huang, Peng Liu
The adaptor protein NUMB is involved in asymmetric division and cell fate determination and recognized as an antagonist of Notch. Previous studies have proved that Notch activation in osteoblasts contributes to a high bone mass. In this study,  however, an osteopenic phenotype was found in 9-week-old mice using osteoblastic specific  Col1a1-2.3-Cre to ablate both Numb and its homologue Numbl . The trabecular bone mass decreased dramatically while the cortical bone mass was unaffected. Here, the Notch signal was not activated, while the tensin homologue deleted on human chromosome 10 (PTEN), which dephosphorylates phosphatidylinositide 3-kinases, was elevated, attenuating protein kinase B (Akt)...
2018: Bone Research
Ke Zhang, Suping Wang, Chenchen Zhou, Lei Cheng, Xianling Gao, Xianju Xie, Jirun Sun, Haohao Wang, Michael D Weir, Mark A Reynolds, Ning Zhang, Yuxing Bai, Hockin H K Xu
Hard tissue repair and regeneration cost hundreds of billions of dollars annually worldwide, and the need has substantially increased as the population has aged. Hard tissues include bone and tooth structures that contain calcium phosphate minerals. Smart biomaterial-based tissue engineering and regenerative medicine methods have the exciting potential to meet this urgent need. Smart biomaterials and constructs refer to biomaterials and constructs that possess instructive/inductive or triggering/stimulating effects on cells and tissues by engineering the material's responsiveness to internal or external stimuli or have intelligently tailored properties and functions that can promote tissue repair and regeneration...
2018: Bone Research
Yuxing Guo, Yuan Yuan, Ling Wu, Thach-Vu Ho, Junjun Jing, Hideki Sugii, Jingyuan Li, Xia Han, Jifan Feng, Chuanbin Guo, Yang Chai
Calvarial bones are connected by fibrous sutures. These sutures provide a niche environment that includes mesenchymal stem cells (MSCs), osteoblasts, and osteoclasts, which help maintain calvarial bone homeostasis and repair. Abnormal function of osteogenic cells or diminished MSCs within the cranial suture can lead to skull defects, such as craniosynostosis. Despite the important function of each of these cell types within the cranial suture, we have limited knowledge about the role that crosstalk between them may play in regulating calvarial bone homeostasis and injury repair...
2018: Bone Research
J Edward Puzas
No abstract text is available yet for this article.
2018: Bone Research
Ye Li, Xinxin Wang, Jiali Ren, Xiaoshan Wu, Guoqing Li, Zhipeng Fan, Chunmei Zhang, Ang Li, Songlin Wang
Signal transduction between different organs is crucial in the normal development of the human body. As an important medium for signal communication, exosomes can transfer important information, such as microRNAs (miRNAs), from donors to receptors. MiRNAs are known to fine-tune a variety of biological processes, including maxillofacial development; however, the underlying mechanism remains largely unknown. In the present study, transient apoptosis was found to be due to the expression of a miniature swine maxillofacial-specific miRNA, ssc-mir-133b...
2018: Bone Research
Wenjia Liu, Liqiang Zhang, Kun Xuan, Chenghu Hu, Shiyu Liu, Li Liao, Bei Li, Fang Jin, Songtao Shi, Yan Jin
Mutations in the liver/bone/kidney alkaline phosphatase ( Alpl ) gene cause hypophosphatasia (HPP) and early-onset bone dysplasia, suggesting that this gene is a key factor in human bone development. However, how and where Alpl acts in bone ageing is largely unknown. Here, we determined that ablation of Alpl induces prototypical premature bone ageing characteristics, including bone mass loss and marrow fat gain coupled with elevated expression of p16INK4A (p16) and p53 due to senescence and impaired differentiation in mesenchymal stem cells (MSCs)...
2018: Bone Research
Liwei Zheng, Caixia Pi, Jun Zhang, Yi Fan, Chen Cui, Yang Zhou, Jianxun Sun, Quan Yuan, Xin Xu, Ling Ye, Xu Cao, Xuedong Zhou
There is currently no effective medical treatment for temporomandibular joint osteoarthritis (TMJ-OA) due to a limited understanding of its pathogenesis. This study was undertaken to investigate the key role of transforming growth factor-β (TGF-β) signalling in the cartilage and subchondral bone of the TMJ using a temporomandibular joint disorder (TMD) rat model, an ageing mouse model and a Camurati-Engelmann disease (CED) mouse model. In the three animal models, the subchondral bone phenotypes in the mandibular condyles were evaluated by µCT, and changes in TMJ condyles were examined by TRAP staining and immunohistochemical analysis of Osterix and p-Smad2/3...
2018: Bone Research
Ming Dang, Laura Saunders, Xufeng Niu, Yubo Fan, Peter X Ma
Bone tissue engineering is an exciting approach to directly repair bone defects or engineer bone tissue for transplantation. Biomaterials play a pivotal role in providing a template and extracellular environment to support regenerative cells and promote tissue regeneration. A variety of signaling cues have been identified to regulate cellular activity, tissue development, and the healing process. Numerous studies and trials have shown the promise of tissue engineering, but successful translations of bone tissue engineering research into clinical applications have been limited, due in part to a lack of optimal delivery systems for these signals...
2018: Bone Research
M Noelle Knight, Kannan Karuppaiah, Michele Lowe, Sarthak Mohanty, Robert L Zondervan, Sheila Bell, Jaimo Ahn, Kurt D Hankenson
The R-spondin family of proteins are Wnt agonists, and the complete embryonic disruption of Rspo2 results in skeletal developmental defects that recapitulate the phenotype observed with Lrp5/6 deficiency. Previous work has shown that R-spondin-2 ( Rspo2 , RSPO2) is both highly expressed in Wnt-stimulated pre-osteoblasts and its overexpression induces osteoblast differentiation in the same cells, supporting its putative role as a positive autocrine regulator of osteoblastogenesis. However, the role of Rspo2 in regulating osteoblastogenesis and bone formation in postnatal bone has not been explored...
2018: Bone Research
Gang Xi, Christine Wai, Clifford J Rosen, David R Clemmons
Male Igfbp2 - / - mice have a significant reduction in bone mass and administration of a peptide that contains the insulin-like growth factor binding protein-2(IGFBP-2) receptor-binding domain stimulates bone formation in these animals. Female Igfbp2 -/- mice do not have this phenotype but following ovariectomy (OVX) lose more bone than OVX wild-type mice. This suggests that in the absence of estrogen, IGFBP-2 is required to maintain bone mass. Therefore these studies were undertaken to determine if this peptide could stimulate bone acquisition in OVX rats...
2018: Bone Research
Lei Wang, Yu Chai, Changjun Li, Haiyun Liu, Weiping Su, Xiaonan Liu, Bing Yu, Weiqi Lei, Bin Yu, Janet L Crane, Xu Cao, Mei Wan
Low-density lipoprotein receptor-related protein 6 (LRP6) is a co-receptor for Wnt signaling and can be recruited by multiple growth factors/hormones to their receptors facilitating intracellular signaling activation. The ligands that bind directly to LRP6 have not been identified. Here, we report that bioactive oxidized phospholipids (oxPLs) are native ligands of LRP6, but not the closely related LRP5. oxPLs are products of lipid oxidation involving in pathological conditions such as hyperlipidemia, atherosclerosis, and inflammation...
2018: Bone Research
Liwei Zheng, Yong Cao, Shuangfei Ni, Huabin Qi, Zemin Ling, Xin Xu, Xuenong Zou, Tianding Wu, Ruoxian Deng, Bo Hu, Bo Gao, Hao Chen, Yusheng Li, Jianxi Zhu, Francis Tintani, Shadpour Demehri, Amit Jain, Khaled M Kebaish, Shenghui Liao, Cheryle A Séguin, Janet L Crane, Mei Wan, Hongbin Lu, Paul D Sponseller, Lee H Riley, Xuedong Zhou, Jianzhong Hu, Xu Cao
Degenerative disc disease (DDD) is associated with intervertebral disc degeneration of spinal instability. Here, we report that the cilia of nucleus pulposus (NP) cells mediate mechanotransduction to maintain anabolic activity in the discs. We found that mechanical stress promotes transport of parathyroid hormone 1 receptor (PTH1R) to the cilia and enhances parathyroid hormone (PTH) signaling in NP cells. PTH induces transcription of integrin αv β6 to activate the transforming growth factor (TGF)-β-connective tissue growth factor (CCN2)-matrix proteins signaling cascade...
2018: Bone Research
Sung Won Lee, Jee Hyun Rho, Sang Yeob Lee, Won Tae Chung, Yoo Jin Oh, Jung Ha Kim, Seung Hee Yoo, Woo Young Kwon, Ju Yong Bae, Su Young Seo, Hokeun Sun, Hye Young Kim, Young Hyun Yoo
Free fatty acids (FFAs), which are elevated with metabolic syndrome, are considered the principal offender exerting lipotoxicity. Few previous studies have reported a causal relationship between FFAs and osteoarthritis pathogenesis. However, the molecular mechanism by which FFAs exert lipotoxicity and induce osteoarthritis remains largely unknown. We here observed that oleate at the usual clinical range does not exert lipotoxicity while oleate at high pathological ranges exerted lipotoxicity through apoptosis in articular chondrocytes...
2018: Bone Research
Patrick Aghajanian, Subburaman Mohan
There is a worldwide epidemic of skeletal diseases causing not only a public health issue but also accounting for a sizable portion of healthcare expenditures. The vertebrate skeleton is known to be formed by mesenchymal cells condensing into tissue elements (patterning phase) followed by their differentiation into cartilage (chondrocytes) or bone (osteoblasts) cells within the condensations. During the growth and remodeling phase, bone is formed directly via intramembranous ossification or through a cartilage to bone conversion via endochondral ossification routes...
2018: Bone Research
Jin-Xiu Pan, Lei Xiong, Kai Zhao, Peng Zeng, Bo Wang, Fu-Lei Tang, Dong Sun, Hao-Han Guo, Xiao Yang, Shun Cui, Wen-Fang Xia, Lin Mei, Wen-Cheng Xiong
YAP (yes-associated protein) is a transcriptional factor that is negatively regulated by Hippo pathway, a conserved pathway for the development and size control of multiple organs. The exact function of YAP in bone homeostasis remains controversial. Here we provide evidence for YAP's function in promoting osteogenesis, suppressing adipogenesis, and thus maintaining bone homeostasis. YAP is selectively expressed in osteoblast (OB)-lineage cells. Conditionally knocking out Yap in the OB lineage in mice reduces cell proliferation and OB differentiation and increases adipocyte formation, resulting in a trabecular bone loss...
2018: Bone Research
Babita Madan, Mitchell J McDonald, Gabrielle E Foxa, Cassandra R Diegel, Bart O Williams, David M Virshup
Dysregulated Wnt signaling is associated with the pathogenesis of cancers, fibrosis, and vascular diseases. Inhibition of Wnt signaling has shown efficacy in various pre-clinical models of these disorders. One of the key challenges in developing targeted anti-cancer drugs is to balance efficacy with on-target toxicity. Given the crucial role Wnts play in the differentiation of osteoblasts and osteoclasts, acute inhibition of Wnt signaling is likely to affect bone homeostasis. In this study, we evaluated the skeletal effect of small molecule inhibitor of an o-acyl transferase porcupine (PORCN) that prevents Wnt signaling by blocking the secretion of all Wnts...
2018: Bone Research
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