Heather Fairfield, Clifford J Rosen, Michaela R Reagan
{"title":"Connecting Bone and Fat: The Potential Role for Sclerostin.","authors":"Heather Fairfield, Clifford J Rosen, Michaela R Reagan","doi":"10.1007/s40610-017-0057-7","DOIUrl":"10.1007/s40610-017-0057-7","url":null,"abstract":"<p><p>Sclerostin (SOST), a protein secreted from mature osteocytes in response to mechanical unloading and other stimuli, inhibits the osteogenic Wnt/β-catenin pathway in mesenchymal stem cells (MSCs) impeding their ability to differentiate into mineralizing osteoblasts.</p><p><strong>Purpose: </strong>This review summarizes the crosstalk between adipose tissue and bone. It also reviews the origin, regulation, and role of SOST in osteogenesis and brings attention to an emerging role of this protein in the regulation of adipogenesis.</p><p><strong>Recent findings: </strong>Bone-derived molecules that drive MSC adipogenesis have not previously been identified, but recent findings suggest that SOST signaling may induce adipogenesis. <i>In vivo</i> SOST acts locally to induce changes in bone and, <i>in vitro,</i> increases adipogenesis in 3T3-L1 preadipocytes.</p><p><strong>Summary: </strong>SOST is able to induce adipogenesis in certain preadipocytes, however bone-specific studies are needed to determine the effect of local SOST concentrations in healthy and disease models on bone marrow adipose tissue.</p>","PeriodicalId":72737,"journal":{"name":"Current molecular biology reports","volume":"3 2","pages":"114-121"},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5448707/pdf/nihms869329.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35060959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Control of the Osteoblast Lineage by Mitogen-Activated Protein Kinase Signaling.","authors":"Renny T Franceschi, Chunxi Ge","doi":"10.1007/s40610-017-0059-5","DOIUrl":"https://doi.org/10.1007/s40610-017-0059-5","url":null,"abstract":"<p><strong>Purpose of the review: </strong>This review will provide a timely assessment of MAP kinase actions in bone development and homeostasis with particular emphasis on transcriptional control of the osteoblast lineage.</p><p><strong>Recent findings: </strong>ERK and p38 MAP kinases function as transducers of signals initiated by the extracellular matrix, mechanical loading, TGF-β, BMPs and FGF2. MAPK signals may also affect and/or interact with other important pathways such as WNT and HIPPO. ERK and p38 MAP kinase pathways phosphorylate specific osteogenic transcription factors including RUNX2, Osterix, ATF4 and DLX5. For RUNX2, phosphorylation at specific serine residues initiates epigenetic changes in chromatin necessary for decondensation and increased transcription. MAPK also suppresses marrow adipogenesis by phosphorylating and inhibiting PPARγ, which may explain the well-known relationship between reduced skeletal loading and marrow fat accumulation.</p><p><strong>Summary: </strong>MAPKs transduce signals from the extracellular environment to the nucleus allowing bone cells to respond to changes in hormonal/growth factor signaling and mechanical loading thereby optimizing bone structure to meet physiological and mechanical needs of the body.</p>","PeriodicalId":72737,"journal":{"name":"Current molecular biology reports","volume":"3 2","pages":"122-132"},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40610-017-0059-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35473342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lilian I Plotkin, Rafael Pacheco-Costa, Hannah M Davis
{"title":"microRNAs and connexins in bone: interaction and mechanisms of delivery.","authors":"Lilian I Plotkin, Rafael Pacheco-Costa, Hannah M Davis","doi":"10.1007/s40610-017-0058-6","DOIUrl":"https://doi.org/10.1007/s40610-017-0058-6","url":null,"abstract":"<p><strong>Purpose of review: </strong>To describe the current knowledge on the cross-talk between connexins and microRNAs (miRs) in bone cells.</p><p><strong>Recent findings: </strong>Connexins play a crucial role on bone development and maintenance, and disruptions in their abundance or localization can affect how bone perceives and responds to mechanical, hormonal, and pharmacological stimuli. Connexin expression can be modified by miRs, which modulate connexin mRNA and protein levels. Recently, different manners by which miRs and connexins can interact in bone have been identified, including mechanisms that mediate miR exchange between cells in direct contact through gap junctions, or between distant cells via extracellular vesicles (EVs).</p><p><strong>Summary: </strong>We bring to light the relationship between miRs and connexins in bone tissue, with special focus on regulatory effects of miRs and connexins on gene expression, as well as the mechanisms that mediate miR exchange between cells in direct contact through gap junctions, or between distant cells via EVs.</p>","PeriodicalId":72737,"journal":{"name":"Current molecular biology reports","volume":"3 2","pages":"63-70"},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40610-017-0058-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35473341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The osteoblastic niche in hematopoiesis and hematological myeloid malignancies.","authors":"Marta Galán-Díez, Stavroula Kousteni","doi":"10.1007/s40610-017-0055-9","DOIUrl":"10.1007/s40610-017-0055-9","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review focuses on evidence highlighting the bidirectional crosstalk between the hematopoietic stem cell (HSC) and their surrounding stromal cells, with a particular emphasis on cells of the osteoblast lineage. The role and molecular functions of osteoblasts in normal hematopoiesis and in myeloid hematological malignancies is discussed.</p><p><strong>Recent findings: </strong>Cells of the osteoblast lineage have emerged as potent regulators of HSC expansion that regulate their recruitment and, depending on their stage of differentiation, their activity, proliferation and differentiation along the lymphoid, myeloid and erythroid lineages. In addition, mutations in mature osteoblasts or their progenitors induce myeloid malignancies. Conversely, signals from myelodysplastic cells can remodel the osteoblastic niche to favor self-perpetuation.</p><p><strong>Summary: </strong>Understanding cellular crosstalk between osteoblastic cells and HSCs in the bone marrow microenvironment is of fundamental importance for developing therapies against benign and malignant hematological diseases.</p>","PeriodicalId":72737,"journal":{"name":"Current molecular biology reports","volume":"3 2","pages":"53-62"},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40610-017-0055-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35518191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reciprocal regulation of PPARγ and RUNX2 activities in marrow mesenchymal stem cells: Fine balance between p38 MAPK and Protein Phosphatase 5.","authors":"Lance A Stechschulte, Beata Lecka-Czernik","doi":"10.1007/s40610-017-0056-8","DOIUrl":"https://doi.org/10.1007/s40610-017-0056-8","url":null,"abstract":"<p><strong>Purpose of review: </strong>Post-translational modifications (PTMs), specifically serine phosphorylation, are essential for determination and tuning up an activity of many proteins, including those that are involved in the control of gene transcription. Transcription factors PPARγ2 and RUNX2 are essential for mesenchymal stem cell (MSC) commitment to either adipocyte or osteoblast lineage. This review is summarizing current knowledge how serine phosphorylation PTMs regulate activities of both transcription factors and MSCs lineage commitment.</p><p><strong>Recent finding: </strong>Both PPARγ2 and RUNX2 transcriptional activities are regulated by similar PTMs, however with an opposite outcome. The same p38 MAPK mediates serine phosphorylation that leads to activation of RUNX2 and inactivation of PPARγ2. The process of protein phosphorylation is balanced with a process of protein dephosphorylation. Protein phosphatase 5 simultaneously dephosphorylates both proteins, which results in activation of PPARγ2 and inactivation of RUNX2.</p><p><strong>Summary: </strong>This review provides a summary of the \"yinyang\" fine-tuned mechanism by which p38 MAPK and PP5 regulate MSCs lineage commitment.</p>","PeriodicalId":72737,"journal":{"name":"Current molecular biology reports","volume":"3 2","pages":"107-113"},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40610-017-0056-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35687478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bone Lining Cells: Normal Physiology and Role in Response to Anabolic Osteoporosis Treatments","authors":"Marc N. Wein","doi":"10.1007/s40610-017-0062-x","DOIUrl":"https://doi.org/10.1007/s40610-017-0062-x","url":null,"abstract":"","PeriodicalId":72737,"journal":{"name":"Current molecular biology reports","volume":"3 1","pages":"79 - 84"},"PeriodicalIF":0.0,"publicationDate":"2017-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40610-017-0062-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45519392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recent Advances in Understanding Histone Modification Events","authors":"Matthew V. Holt, Tao Wang, N. L. Young","doi":"10.1007/s40610-017-0050-1","DOIUrl":"https://doi.org/10.1007/s40610-017-0050-1","url":null,"abstract":"","PeriodicalId":72737,"journal":{"name":"Current molecular biology reports","volume":"3 1","pages":"11 - 17"},"PeriodicalIF":0.0,"publicationDate":"2017-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40610-017-0050-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"52668179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recombinant Plant Engineering for Immunotherapeutic Production.","authors":"Ankit Singh, Gurminder Kaur, Sanchita Singh, Neetu Singh, Gauri Saxena, Praveen C Verma","doi":"10.1007/s40610-017-0078-2","DOIUrl":"10.1007/s40610-017-0078-2","url":null,"abstract":"<p><strong>Purpose of review: </strong>The requirement for large quantities of therapeutic proteins has fueled a great interest in the production of recombinant proteins in plant bioreactors. The vaccines and bio-therapeutic protein production in plants hold the promise of significantly lowering the cost of manufacturing life-saving drugs. This review will reflect the current status and challenges that the molecular farming platform faces becoming a strategic solution for the development of low-cost bio-therapeutics for developing countries.</p><p><strong>Recent findings: </strong>Different plant parts have been successfully identified as suitable expression systems for the commercial production of therapeutic proteins for some human and animal diseases ranging from common cold to AIDS. The processed therapeutics from such sources are devoid of any toxic components. The large-scale cultivation of these transgenic plants would be possible anywhere in the world including developing countries, which lack sophisticated drug manufacturing units. A couple of such commercially generated products have already hit the market with success. Newer methods using suitable plant viruses and recombinant gene expression systems have already been devised for producing therapeutic proteins and peptides.</p><p><strong>Summary: </strong>Plants are promising bio-factories for therapeutic protein production because of their several advantages over the other expression systems especially the advanced mechanisms for protein synthesis and post-translational modification which are very much similar to animal cells. Plant biotechnologists are much attracted to the bio-farming because of its flexibility, scalability, low manufacturing cost, as well as the lack of risk of toxic or pathogenic contamination. A number of projects on bio-farming are designed and are at various developmental stages but have not yet become available to the pharmaceutical industry. Therefore, we need further advancement in the optimization of lab protocols for up-scaling the production of such therapeutics at commercial level with a promise to offer their best clinical use.</p>","PeriodicalId":72737,"journal":{"name":"Current molecular biology reports","volume":"3 4","pages":"306-316"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40610-017-0078-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37783301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}