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1. Mechanoregulation of MSC spheroid immunomodulation

Author

Thai, Victoria L, Mierswa, Sabrina, Griffin, Katherine H, Boerckel, Joel D, and Leach, J Kent

Subjects
Engineering, Biomedical Engineering, Regenerative Medicine, Underpinning research, 5.2 Cellular and gene therapies, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Aetiology, Development of treatments and therapeutic interventions, Biomedical engineering
Abstract

Mesenchymal stromal cells (MSCs) are widely used in cell-based therapies and tissue regeneration for their potent secretome, which promotes host cell recruitment and modulates inflammation. Compared to monodisperse cells, MSC spheroids exhibit improved viability and increased secretion of immunomodulatory cytokines. While mechanical stimulation of monodisperse cells can increase cytokine production, the influence of mechanical loading on MSC spheroids is unknown. Here, we evaluated the effect of controlled, uniaxial cyclic compression on the secretion of immunomodulatory cytokines by human MSC spheroids and tested the influence of load-induced gene expression on MSC mechanoresponsiveness. We exposed MSC spheroids, entrapped in alginate hydrogels, to three cyclic compressive regimes with varying stress (L) magnitudes (i.e., 5 and 10 kPa) and hold (H) durations (i.e., 30 and 250 s) L5H30, L10H30, and L10H250. We observed changes in cytokine and chemokine expression dependent on the loading regime, where higher stress regimes tended to result in more exaggerated changes. However, only MSC spheroids exposed to L10H30 induced human THP-1 macrophage polarization toward an M2 phenotype compared to static conditions. Static and L10H30 loading facilitated a strong, interlinked F-actin arrangement, while L5H30 and L10H250 disrupted the structure of actin filaments. This was further examined when the actin cytoskeleton was disrupted via Y-27632. We observed downregulation of YAP-related genes, and the levels of secreted inflammatory cytokines were globally decreased. These findings emphasize the essential role of mechanosignaling in mediating the immunomodulatory potential of MSC spheroids.

Published
2024

4. Pathogenesis, Symptomatology, and Transmission of SARS-CoV-2 through Analysis of Viral Genomics and Structure

Author

Rando, Halie M., MacLean, Adam L., Lee, Alexandra J., Lordan, Ronan, Ray, Sandipan, Bansal, Vikas, Skelly, Ashwin N., Sell, Elizabeth, Dziak, John J., Shinholster, Lamonica, McGowan, Lucy D'Agostino, Guebila, Marouen Ben, Wellhausen, Nils, Knyazev, Sergey, Boca, Simina M., Capone, Stephen, Qi, Yanjun, Park, YoSon, Sun, Yuchen, Mai, David, Boerckel, Joel D., Brueffer, Christian, Byrd, James Brian, Kamil, Jeremy P., Wang, Jinhui, Velazquez, Ryan, Szeto, Gregory L, Barton, John P., Goel, Rishi Raj, Mangul, Serghei, Lubiana, Tiago, Consortium, COVID-19 Review, Gitter, Anthony, and Greene, Casey S.

Subjects
Quantitative Biology - Quantitative Methods
Abstract

The novel coronavirus SARS-CoV-2, which emerged in late 2019, has since spread around the world and infected hundreds of millions of people with coronavirus disease 2019 (COVID-19). While this viral species was unknown prior to January 2020, its similarity to other coronaviruses that infect humans has allowed for rapid insight into the mechanisms that it uses to infect human hosts, as well as the ways in which the human immune system can respond. Here, we contextualize SARS-CoV-2 among other coronaviruses and identify what is known and what can be inferred about its behavior once inside a human host. Because the genomic content of coronaviruses, which specifies the virus's structure, is highly conserved, early genomic analysis provided a significant head start in predicting viral pathogenesis and in understanding potential differences among variants. The pathogenesis of the virus offers insights into symptomatology, transmission, and individual susceptibility. Additionally, prior research into interactions between the human immune system and coronaviruses has identified how these viruses can evade the immune system's protective mechanisms. We also explore systems-level research into the regulatory and proteomic effects of SARS-CoV-2 infection and the immune response. Understanding the structure and behavior of the virus serves to contextualize the many facets of the COVID-19 pandemic and can influence efforts to control the virus and treat the disease.

Published
2021
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5. Pathogenesis, Symptomatology, and Transmission of SARS-CoV-2 through Analysis of Viral Genomics and Structure.

Author

Rando, Halie M, MacLean, Adam L, Lee, Alexandra J, Lordan, Ronan, Ray, Sandipan, Bansal, Vikas, Skelly, Ashwin N, Sell, Elizabeth, Dziak, John J, Shinholster, Lamonica, McGowan, Lucy D'Agostino, Guebila, Marouen Ben, Wellhausen, Nils, Knyazev, Sergey, Boca, Simina M, Capone, Stephen, Qi, Yanjun, Park, YoSon, Sun, Yuchen, Mai, David, Boerckel, Joel D, Brueffer, Christian, Byrd, James Brian, Kamil, Jeremy P, Wang, Jinhui, Velazquez, Ryan, Szeto, Gregory L, Barton, John P, Goel, Rishi Raj, Mangul, Serghei, Lubiana, Tiago, Consortium, Covid-Review, Gitter, Anthony, and Greene, Casey S

Subjects
Vaccine Related, Pneumonia, Lung, Infectious Diseases, Emerging Infectious Diseases, Prevention, Pneumonia & Influenza, Biotechnology, Biodefense, 2.2 Factors relating to the physical environment, Aetiology, 2.1 Biological and endogenous factors, Infection, Good Health and Well Being, COVID-19, genomics, review, viral pathogenesis, COVID-19 Review Consortium Vikas Bansal, John P. Barton, Simina M. Boca, Joel D. Boerckel, Christian Brueffer, James Brian Byrd, Stephen Capone, Shikta Das, Anna Ada Dattoli, John J. Dziak, Jeffrey M. Field, Soumita Ghosh, Anthony Gitter, Rishi Raj Goel, Casey S. Greene, Marouen Ben Guebila, Daniel S. Himmelstein, Fengling Hu, Nafisa M. Jadavji, Jeremy P. Kamil, Sergey Knyazev, Likhitha Kolla, Alexandra J. Lee, Ronan Lordan, Tiago Lubiana, Temitayo Lukan, Adam L. MacLean, David Mai, Serghei Mangul, David Manheim, Lucy D’Agostino McGowan, Amruta Naik, YoSon Park, Dimitri Perrin, Yanjun Qi, Diane N. Rafizadeh, Bharath Ramsundar, Halie M. Rando, Sandipan Ray, Michael P. Robson, Vincent Rubinetti, Elizabeth Sell, Lamonica Shinholster, Ashwin N. Skelly, Yuchen Sun, Yusha Sun, Gregory L. Szeto, Ryan Velazquez, Jinhui Wang, Nils Wellhausen
Abstract

The novel coronavirus SARS-CoV-2, which emerged in late 2019, has since spread around the world and infected hundreds of millions of people with coronavirus disease 2019 (COVID-19). While this viral species was unknown prior to January 2020, its similarity to other coronaviruses that infect humans has allowed for rapid insight into the mechanisms that it uses to infect human hosts, as well as the ways in which the human immune system can respond. Here, we contextualize SARS-CoV-2 among other coronaviruses and identify what is known and what can be inferred about its behavior once inside a human host. Because the genomic content of coronaviruses, which specifies the virus's structure, is highly conserved, early genomic analysis provided a significant head start in predicting viral pathogenesis and in understanding potential differences among variants. The pathogenesis of the virus offers insights into symptomatology, transmission, and individual susceptibility. Additionally, prior research into interactions between the human immune system and coronaviruses has identified how these viruses can evade the immune system's protective mechanisms. We also explore systems-level research into the regulatory and proteomic effects of SARS-CoV-2 infection and the immune response. Understanding the structure and behavior of the virus serves to contextualize the many facets of the COVID-19 pandemic and can influence efforts to control the virus and treat the disease. IMPORTANCE COVID-19 involves a number of organ systems and can present with a wide range of symptoms. From how the virus infects cells to how it spreads between people, the available research suggests that these patterns are very similar to those seen in the closely related viruses SARS-CoV-1 and possibly Middle East respiratory syndrome-related CoV (MERS-CoV). Understanding the pathogenesis of the SARS-CoV-2 virus also contextualizes how the different biological systems affected by COVID-19 connect. Exploring the structure, phylogeny, and pathogenesis of the virus therefore helps to guide interpretation of the broader impacts of the virus on the human body and on human populations. For this reason, an in-depth exploration of viral mechanisms is critical to a robust understanding of SARS-CoV-2 and, potentially, future emergent human CoVs (HCoVs).

Published
2021

7. Super-resolution fluorescence microscopy by stepwise optical saturation

Author

Zhang, Yide, Nallathamby, Prakash D., Vigil, Genevieve D., Khan, Aamir A., Mason, Devon E., Boerckel, Joel D., Roeder, Ryan K., and Howard, Scott S.

Subjects
Physics - Optics, Physics - Biological Physics
Abstract

Super-resolution fluorescence microscopy is an important tool in biomedical research for its ability to discern features smaller than the diffraction limit. However, due to its difficult implementation and high cost, the universal application of super-resolution microscopy is not feasible. In this paper, we propose and demonstrate a new kind of super-resolution fluorescence microscopy that can be easily implemented and requires neither additional hardware nor complex post-processing. The microscopy is based on the principle of stepwise optical saturation (SOS), where $M$ steps of raw fluorescence images are linearly combined to generate an image with a $\sqrt{M}$-fold increase in resolution compared with conventional diffraction-limited images. For example, linearly combining (scaling and subtracting) two images obtained at regular powers extends resolution by a factor of $1.4$ beyond the diffraction limit. The resolution improvement in SOS microscopy is theoretically infinite but practically is limited by the signal-to-noise ratio. We perform simulations and experimentally demonstrate super-resolution microscopy with both one-photon (confocal) and multiphoton excitation fluorescence. We show that with the multiphoton modality, the SOS microscopy can provide super-resolution imaging deep in scattering samples., Comment: 14 pages, 10 figures, 1 table

Published
2018
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8. Virtual screening for small-molecule pathway regulators by image-profile matching

Author

Rohban, Mohammad H., Fuller, Ashley M., Tan, Ceryl, Goldstein, Jonathan T., Syangtan, Deepsing, Gutnick, Amos, DeVine, Ann, Nijsure, Madhura P., Rigby, Megan, Sacher, Joshua R., Corsello, Steven M., Peppler, Grace B., Bogaczynska, Marta, Boghossian, Andrew, Ciotti, Gabrielle E., Hands, Allison T., Mekareeya, Aroonroj, Doan, Minh, Gale, Jennifer P., Derynck, Rik, Turbyville, Thomas, Boerckel, Joel D., Singh, Shantanu, Kiessling, Laura L., Schwarz, Thomas L., Varelas, Xaralabos, Wagner, Florence F., Kafri, Ran, Eisinger-Mathason, T.S. Karin, and Carpenter, Anne E.

Published
2022
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12. Moesin activation controls bone resorption and tunneling nanotube-dependent osteoclast fusion

Author

Dufrancais, Ophelie, primary, Verdys, Perrine, additional, Metais, Arnaud, additional, Juzans, Marie, additional, Sanchez, Thibaut, additional, Bergert, Martin, additional, Plozza, Marianna, additional, Halper, Julia, additional, Panebianco, Christopher J, additional, Mascarau, Remi, additional, Gence, Remi, additional, Arnaud, Gaelle, additional, Ben Neji, Myriam, additional, Maridonneau-Parini, Isabelle, additional, Le Cabec, Veronique, additional, Boerckel, Joel D, additional, Pavlos, Nathan, additional, Diz-Munoz, Alba, additional, Lagarrigue, Frederic, additional, Blin-Wakkach, Claudine, additional, Carreno, Sebastien, additional, Poincloux, Renaud, additional, Burkhardt, Janis K., additional, Raynaud-Messina, Brigitte, additional, and Verollet, Christel, additional

Published
2024
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16. YAP and TAZ couple osteoblast precursor mobilization to angiogenesis and mechanoregulation in murine bone development

Author

Collins, Joseph M., primary, Lang, Annemarie, additional, Parisi, Cristian, additional, Moharrer, Yasaman, additional, Nijsure, Madhura P., additional, (Thomas) Kim, Jong Hyun, additional, Ahmed, Saima, additional, Szeto, Gregory L., additional, Qin, Ling, additional, Gottardi, Riccardo, additional, Dyment, Nathaniel A., additional, Nowlan, Niamh C., additional, and Boerckel, Joel D., additional

Published
2023
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21. Mechanoepigenetic regulation of extracellular matrix homeostasis via Yap and Taz

Author

Jones, Dakota L., primary, Hallström, Grey F., additional, Jiang, Xi, additional, Locke, Ryan C., additional, Evans, Mary Kate, additional, Bonnevie, Edward D., additional, Srikumar, Anjana, additional, Leahy, Thomas P., additional, Nijsure, Madhura P., additional, Boerckel, Joel D., additional, Mauck, Robert L., additional, and Dyment, Nathaniel A., additional

Published
2023
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22. YAP and TAZ couple osteoblast precursor mobilization to angiogenesis and mechanoregulated bone development

Author

Collins, Joseph M., primary, Lang, Annemarie, additional, Parisi, Cristian, additional, Moharrer, Yasaman, additional, Nijsure, Madhura P., additional, Kim, Jong Hyun (Thomas), additional, Szeto, Greg L., additional, Qin, Ling, additional, Gottardi, Riccardo L., additional, Dyment, Nathanial A., additional, Nowlan, Niamh C., additional, and Boerckel, Joel D., additional

Published
2023
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24. YAP and TAZ Couple Osteoblast Precursor Mobilization to Angiogenesis and Mechanoregulation in Fetal Bone Development

Author

Collins, Joseph, primary, Lang, Annemarie, additional, Parisi, Cristian, additional, Moharrer, Yasaman, additional, Nijsure, Madhura P., additional, Kim, Jong Hyun (Thomas), additional, Ahmed, Saima, additional, Szeto, Gregory L., additional, Qin, Ling, additional, Gottardi, Riccardo L., additional, Dyment, Nathaniel A., additional, Nowlan, Niamh C., additional, and Boerckel, Joel D., additional

Published
2023
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25. Contributors

Author

Agarwal, Rachit, primary, Ahlstrom, Jon D., additional, Ahmad, Rafiq, additional, Alarcon, Emilio I., additional, Almarza, Alejandro J., additional, Almeida-Porada, Graça, additional, Almeida, Manuel, additional, Alvarado-Velez, Melissa, additional, Anderson, James M., additional, Arcidiacono, Judith, additional, Atala, Anthony, additional, Badylak, Stephen F., additional, Balkan, Wayne, additional, Ballios, Brian G., additional, Baptista, Pedro M., additional, Baumann, M. Douglas, additional, Bedi, Supinder S., additional, Bellamkonda, Ravi V., additional, Bergmann, Nicole M., additional, Blau, Helen M., additional, Boerckel, Joel D., additional, Bratt-Leal, Andres M., additional, Brown, James C., additional, Brubaker, Scott, additional, Brunette, Isabelle, additional, Calderon, Gisele A., additional, Caplan, Arnold I., additional, Castner, David G., additional, Chang, Cynthia, additional, Chawla, Aditya, additional, Chen, Xuguang, additional, Cohen, Paul, additional, Cooke, Michael J., additional, Copus, Joshua S., additional, Correlo, Vitor M., additional, Cox, Charles S., additional, Dahl, Abritee, additional, Day, Richard M., additional, De Coppi, Paolo, additional, Dodla, Mahesh C., additional, Elisseeff, Jennifer H., additional, Emamaullee, Juliet A., additional, Esa, Adam, additional, Fang, Yunlan, additional, Faust, Heather J., additional, Fisher, John P., additional, Fisher, Matthew B., additional, Francois, Elvis L., additional, García, Andrés J., additional, Gavrilov, Svetlana, additional, Gazit, Dan, additional, Gazit, Zulma, additional, Gemmiti, Christopher V., additional, Gillispie, Gregory J., additional, Gilpin, Sarah E., additional, Godbey, W.T., additional, Gray, Andrea, additional, Green, Ronald M., additional, Griffith, May, additional, Guldberg, Robert E., additional, Guo, Qiongyu, additional, Gurtner, Geoffrey C., additional, Hacker, Michael C., additional, Hanna, Issa A., additional, Hare, Joshua M., additional, Hatzistergos, Konstantinos E., additional, Herber, Ralf-Peter, additional, Hilborn, Jöns, additional, Humes, H. David, additional, Hunsberger, Joshua G., additional, Iwasa, Kenjiro, additional, Jackson, John D., additional, Jackson, Margaret L., additional, Jang, Hae Lin, additional, Jansen, John A., additional, Johnston, Josephine, additional, Jorns, Carl, additional, Kang, Huijun, additional, Kaplan, David L., additional, Kaplan, David S., additional, Katz, Adam J., additional, Kelley, Matthew W., additional, Kennedy, Kelsey, additional, Khademhosseini, Ali, additional, Khang, Gilson, additional, Kim, Jinho, additional, Klein, Rachel H., additional, Klimanskaya, Irina, additional, Knoepfler, Paul S., additional, Ko, In Kap, additional, Kolambkar, Yash M., additional, Krieghoff, Jan, additional, Kucko, Nathan W., additional, Kumar, Manoj, additional, Kurtzberg, Joanne, additional, Kwilas, Anna, additional, Landry, Donald W., additional, Langhans, Mark T., additional, Lanza, Robert, additional, Lanzoni, Giacomo, additional, Lee, Sang Jin, additional, Leeuwenburgh, Sander C.G., additional, Leong, Kam W., additional, Liang, Rui, additional, Liaudanskaya, Volha, additional, Lin, Hang, additional, Longaker, Michael T., additional, Lorenz, Hermann P., additional, Loring, Jeanne F., additional, Lu, Shi-Jiang, additional, Lue, Alberto, additional, Ma, Peter X., additional, Magalhaes, Renata S., additional, Mandla, Serena, additional, Marshall, Clement D., additional, Martins-Green, Manuela, additional, Mason, Devon E., additional, Mau, Jonquil R., additional, McFarland, Richard, additional, McHale, Melissa K., additional, Melville, James C., additional, Meyers, Jason R., additional, Mikos, Antonios G., additional, Miller, Jordan S., additional, Mittermiller, Paul A., additional, Miyachi, Hideki, additional, Miyamoto, Shinka, additional, Monteiro, Nelson, additional, Moore, Alessandra L., additional, Morini, Sara, additional, Moser, Philipp T., additional, Mukhatyar, Vivek J., additional, Murdock, Mark, additional, Nagiel, Aaron, additional, Naughton, Gail K., additional, Nauta, Allison, additional, Navarro, Javier, additional, Newton, Jared M., additional, Nori, Aparna, additional, Okano, Teruo, additional, Oliveira, Joaquim M., additional, Ott, Harald C., additional, Padmanabhan, Jagannath, additional, Page, Kristin M., additional, Pallickaveedu Rajan Asari, Anil Kumar, additional, Papaioannou, Virginia E., additional, Park, Jihoon, additional, Payne, Samantha L., additional, Pelled, Gadi, additional, Pepper, Andrew, additional, Perumal, Elumalai, additional, Petreaca, Melissa, additional, Pino, Christopher J., additional, Pirosa, Alessandro, additional, Pla-Palacín, Iris, additional, Pokrywczynska, Marta, additional, Porada, Christopher D., additional, Porter, Blaise D., additional, Radisic, Milica, additional, Rambhia, Kunal J., additional, Raquel Maia, F., additional, Ratner, Buddy D., additional, Reddi, A.H., additional, Reis, Rui L., additional, Ricles, Laura, additional, Ricordi, Camillo, additional, Rizwan, Muhammad, additional, Robinson, Rebecca, additional, Rodrigues, Melanie, additional, Rothrauff, Benjamin B., additional, Sadri-Ardekani, Hooman, additional, Sainz-Arnal, Pilar, additional, Sambathkumar, Rangarajan, additional, Sánchez-Romero, Natalia, additional, Scarritt, Michelle, additional, Schneider, Christopher M., additional, Schwartz, Steven D., additional, Selem, Sarah, additional, Serrano-Aulló, Trinidad, additional, Shapiro, A.M. James, additional, Sheyn, Dmitriy, additional, Shimizu, Tatsuya, additional, Shinoka, Toshiharu, additional, Shoichet, Molly S., additional, Shoji, Toshihiro, additional, Shupe, Thomas, additional, Sikora, Andrew G., additional, Simpson, Fiona, additional, Skardal, Aleksander, additional, Skuk, Daniel, additional, Smith, Brandon T., additional, Sohn, Jihee, additional, Soker, Shay, additional, Solanas, Estela, additional, Song, Jeong Eun, additional, Sood, Disha, additional, Stocum, David L., additional, Strom, Stephen C., additional, Sun, Jessica M., additional, Takahashi, Hironobu, additional, Tremblay, Jacques P., additional, Tripathy, Nirmalya, additional, Tse, John W., additional, Tuan, Rocky S., additional, Verfaillie, Catherine M., additional, Vunjak-Novakovic, Gordana, additional, Wagner, William R., additional, Wang, Yanling, additional, Watson, Emma, additional, West, Jennifer L., additional, Williams, David F., additional, Williams, James K., additional, Wong, Mark E., additional, Woo, Savio L-Y., additional, Wood, Fiona M., additional, Xu, Lei, additional, Yakubovich, Doron C., additional, Yang, Yafeng, additional, Yaszemski, Michael J., additional, Yelick, Pamela C., additional, Yim, Evelyn K.F., additional, Yong, Carolyn, additional, Yoo, James J., additional, Young, Simon, additional, Yucel, Nora, additional, Zacharias, Rachel L., additional, Zhang, Yuanyuan, additional, Zhang, Ai, additional, Zhang, Jin, additional, and Zhu, Yang, additional

Published
2018
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31. Stress vesicles are induced by acute mechanical force and precede the commitment of epidermal stem cells to terminal differentiation

Author

Huang, Sixia, primary, Kuri, Paola, additional, Zou, Jonathan, additional, Blanco, Adriana, additional, Marshall, Maxwell, additional, Rice, Gabriella, additional, Prouty, Stephen, additional, Dentchev, Tzvete, additional, Doepner, Miriam, additional, Boerckel, Joel D., additional, Capell, Brian C., additional, Ridky, Todd W., additional, and Rompolas, Panteleimon, additional

Published
2022
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40. Correction for Rando et al., 'Pathogenesis, Symptomatology, and Transmission of SARS-CoV-2 through Analysis of Viral Genomics and Structure'

Author

Rando, Halie M, MacLean, Adam L, D'Agostino McGowan, Lucy, Ben Guebila, Marouen, Wellhausen, Nils, Knyazev, Sergey, Boca, Simina M, Capone, Stephen, Qi, Yanjun, Park, YoSon, Mai, David, Sun, Yuchen, Lee, Alexandra J, Boerckel, Joel D, Brueffer, Christian, Byrd, James Brian, Kamil, Jeremy P, Wang, Jinhui, Velazquez, Ryan, Szeto, Gregory L, Barton, John P, Goel, Rishi Raj, Mangul, Serghei, Lordan, Ronan, Lubiana, Tiago, Consortium, COVID-19 Review, Gitter, Anthony, Greene, Casey S, Ray, Sandipan, Bansal, Vikas, Skelly, Ashwin N, Sell, Elizabeth, Dziak, John J, and Shinholster, Lamonica

Subjects
Physiology, Modeling and Simulation, ddc:570, Genetics, Molecular Biology, Biochemistry, Microbiology, Ecology, Evolution, Behavior and Systematics, Computer Science Applications
Published
2022
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43. In vivo model for evaluating the effects of mechanical stimulation on tissue-engineered bone repair

Author

Boerckel, Joel D., Dupont, Kenneth M., Kolambkar, Yash M., Lin, Angela S.P., and Guldberg, Robert E.

Subjects
Biomechanics -- Research, Bone regeneration -- Methods, Engineering and manufacturing industries, Science and technology
Abstract

It has long been known that the bone adapts according to the local mechanical environment. To date, however, a model for studying the effects of functional mechanical loading on tissue-engineered bone repair in vivo has not yet been established. We have developed a rat femoral defect model in which ambulatory loads are transduced through the implanted tissue-engineered construct to elucidate the role of the mechanical environment in functional restoration of a large bone defect. This model uses compliant fixation plates with integrated elastomeric segments, which allow transduction of ambulatory loads. Multiaxially and uniaxially compliant plates were characterized by mechanical testing and evaluated using in vivo pilot studies. In the first study, experimental limbs were implanted with multiaxial plates, which have a low stiffness in multiple loading modes. In the second study, experimental limbs were stabilized by a uniaxial plate, which allowed only axial deformation of the defect. X-ray scans and mechanical testing revealed that the multiaxial plates were insufficient to stabilize the defect and prevent fracture under ambulatory loads as a result of low flexural and torsional stiffness. The uniaxial plates, however, maintained integrity of the defect when implanted over a 12 week period. Postmortem micro-CT scans revealed a 19% increase in bone volume in the axially loaded limb compared with the contralateral standard control and postmortem mechanical testing indicated that torsional strength and stiffness were increased 25.6- and 3.9-fold, respectively, compared with the control Finite element modeling revealed high strain gradients in the soft tissue adjacent to the newly formed bone within the implanted construct. This study introduces an in vivo model for studying the effects of physiological mechanical loading on tissue-engineered bone repair. Preliminary results using this new in vivo model with the uniaxially compliant plate showed positive effects of load-bearing on functional defect repair. [DOI: 10.1115/1.3148472] Keywords: bone, tissue engineering, mechanical stimulation, biomechanics

Published
2009

44. BMP-SMAD1/5 Signaling Is Required For Adequate Coupling Of Angiogenesis And Osteogenesis In Long Bones

Author

Lang, Annemarie, Benn, Andreas, Damerau, Alexandra, Boerckel, Joel D., Kerckhofs, Greet, Zwijsen, An, UCL - SST/IMMC/MEED - Mechatronic, Electrical Energy, and Dynamics Systems, Universitätsmedizin Berlin - Department of Rheumatology and Clinical Immunology, Charité, KU Leuven - Center for Molecular and Vascular Biology, University of Pennsylvania - Departments of Orthopaedic Surgery and Bioengineering, KU Leuven - Prometheus, Division of Skeletal Tissue Engineering, and UCL - SSS/IREC - Institut de recherche expérimentale et clinique

Abstract

The bone vasculature is essential for skeletal development, homeostasis, and regeneration. In long bones, specific capillary subtypes couple angiogenesis to osteogenesis, especially at the growth plate (metaphysis) and endosteum. These metaphyseal and endosteal vessels, termed “type H,” express high levels of CD31 and endomucin (CD31hiEmcnhi), show a columnar structure and are closely related to Osterix (Osx)- and Runt-related transcription factor 2 (Runx2)-expressing osteoblasts and their progenitors [1]. Sinusoidal vessels with low expression of CD31 and Emcn (CD31lowEmcnlow, type L vessels) are mainly found in the diaphysis/bone marrow cavity [1]. The crosstalk between endothelial cells (ECs) of type H vessels and bone-related cells is characterized by osteogenesis-promoting factors provided by ECs and angiogenic mediators secreted by osteoblast-lineage cells. Bone morphogenetic proteins (BMP) are major regulators of vessel formation, however their role within angiogenic and osteogenic coupling and in particular, the involvement of BMP-related intracellular effectors SMAD1 and SMAD5 (SMAD1/5) is unclear. Previously, we demonstrated that during mouse embryonic development, the synergy of Notch and SMAD1/5 is responsible for the balanced selection of tip and stalk cells in vascular sprouting [2]. Furthermore, we reported that endothelium-specific deletion of SMAD1/5 during early postnatal retinal angiogenesis resulted in arteriovenous malformations, a reduced number of tip cells and a hyperdensity in the vascular plexus [3]. Therefore, we hypothesized that functional EC-specific SMAD1/5 signaling is required for (i) formation and maturation of long bone vasculature and (ii) coupling of osteogenesis and angiogenesis, specifically of type H vessel formation in the metaphysis.

Published
2021

45. Virtual screening for small molecule pathway regulators by image profile matching

Author

Rohban, Mohammad H., primary, Fuller, Ashley M., additional, Tan, Ceryl, additional, Goldstein, Jonathan T., additional, Syangtan, Deepsing, additional, Gutnick, Amos, additional, DeVine, Ann, additional, Nijsure, Madhura P., additional, Rigby, Megan, additional, Sacher, Joshua R., additional, Corsello, Steven M., additional, Peppler, Grace B., additional, Bogaczynska, Marta, additional, Boghossian, Andrew, additional, Ciotti, Gabrielle E., additional, Hands, Allison T., additional, Mekareeya, Aroonroj, additional, Doan, Minh, additional, Gale, Jennifer P., additional, Derynck, Rik, additional, Turbyville, Thomas, additional, Boerckel, Joel D., additional, Singh, Shantanu, additional, Kiessling, Laura L., additional, Schwarz, Thomas L., additional, Varelas, Xaralabos, additional, Wagner, Florence F., additional, Kafri, Ran, additional, Eisinger-Mathason, T.S. Karin, additional, and Carpenter, Anne E., additional

Published
2021
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50. Contributors

Author

Aboushwareb, Tamer, primary, Ahlstrom, Jon D., additional, Almarza, Alejandro J., additional, Anderson, James M., additional, Arcidiacono, Judith, additional, Atala, Anthony, additional, Badylak, Stephen F., additional, Bae, Jae Hyun, additional, Ballios, Brian G., additional, Batra, Ashok, additional, Baumann, M. Douglas, additional, Bellamkonda, Ravi V., additional, Bergmann, Nicole M., additional, Bhatia, Mickie, additional, Birchall, Martin A., additional, Blau, Helen M., additional, Boerckel, Joel D., additional, Brivanlou, Ali H., additional, Cananzi, Mara, additional, Caplan, Arnold I., additional, Carnwath, Joseph W., additional, Challen, Grant A., additional, Christ, George J., additional, Chung, Hyun Jung, additional, Colehour, Maegen, additional, Cooke, Michael J., additional, Correlo, V.M., additional, Cosgrove, Benjamin D., additional, Da Sacco, Stefano, additional, Dang, Jiyoung M., additional, Day, Richard M., additional, De Coppi, Paolo, additional, De Filippo, Roger E., additional, Dodla, Mahesh C., additional, Domínguez-Bendala, Juan, additional, Dorin, Ryan P., additional, Durfor, Charles N., additional, Effros, Rita B., additional, Elisseeff, Jennifer H., additional, Ellis, Ewa C.S., additional, Emamaullee, Juliet A., additional, Fagerholm, Per, additional, Feng, Qiang, additional, Fink, Donald, additional, Fisher, Matthew B., additional, García, Andrés J., additional, Gavrilov, Svetlana, additional, Gazit, Dan, additional, Gazit, Zulma, additional, Gemmiti, Christopher V., additional, Gersbach, Charles A., additional, Goodell, Margaret A., additional, Grayeski, Deborah Lavoie, additional, Green, Ronald M., additional, Griffith, May, additional, Guldberg, Robert E., additional, Guo, Qiongyu, additional, Hacker, M.C., additional, Hackett, Joanne, additional, Hare, Joshua M., additional, Harrison, Benjamin S., additional, Hatzistergos, Konstantinos E., additional, Healy, Kevin E., additional, Hilbert, Stephen L., additional, Hu, Jiang, additional, Huber, Alexander, additional, Humes, H. David, additional, Irwin, Elizabeth F., additional, Isenberg, Brett C., additional, Iwata, Takanori, additional, Janes, Sam, additional, Jeng, Lily, additional, Ji, Junfeng, additional, Johnston, Josephine, additional, Johnston, Kimberly A., additional, Kaplan, David L., additional, Kaplan, David S., additional, Karaoglu, Sinan, additional, Katz, Adam J., additional, Kim, Jaehyun, additional, Kimbrel, Erin A., additional, Kimelman, Nadav, additional, Kluge, Jonathan A., additional, Koh, Chester J., additional, Kolambkar, Yash M., additional, Komura, Makoto, additional, Kues, Wilfried A., additional, Ng kee Kwong, Francois, additional, Lagali, Neil, additional, Lamba, Deepak A., additional, Landry, Donald W., additional, Lanza, Robert, additional, Larson, Barrett, additional, Latorre, Malcolm A., additional, Lazarus, Ellen, additional, Lee, Hyukjin, additional, Lee, Mark H., additional, Lee, Sang Jin, additional, Leisk, Gary G., additional, Li, Feng, additional, Liang, Rui, additional, Lin, Kuanyin K., additional, Liu, Xiaohua, additional, Longaker, Michael T., additional, Lorenz, H. Peter, additional, Lu, Shi-Jiang, additional, Lucas-Hahn, Andrea, additional, Ma, Peter X., additional, Macchiarini, Paolo, additional, Machingal, Masood A., additional, Mano, J.F., additional, Martins-Green, M., additional, McCall, Michael, additional, McFarland, Richard, additional, McHale, Melissa K., additional, Mericli, Alexander F., additional, Mikos, A.G., additional, Mukhatyar, Vivek J., additional, Nauta, Allison, additional, Neves, N.M., additional, Niemann, Heiner, additional, Okano, Teruo, additional, Okita, Keisuke, additional, Oliveira, J.M., additional, Papaioannou, Virginia E., additional, Park, Tae Gwan, additional, Pelled, Gadi, additional, Perin, Laura, additional, Petreaca, M., additional, Pileggi, Antonello, additional, Pollock, Jacob F., additional, Porter, Blaise D., additional, Radisic, Milica, additional, Rao, Nandini, additional, Reddi, A.H., additional, Reh, Thomas A., additional, Reis, R.L., additional, Ricordi, Camillo, additional, Roelandt, Philip, additional, Sangan, Caroline Beth, additional, Saul, Justin M., additional, Schaffer, David V., additional, Schuch, Gunter, additional, Sefton, Michael V., additional, Selem, Sarah, additional, Shapiro, A.M. James, additional, Sheardown, Heather, additional, Sheyn, Dima, additional, Shoichet, Molly S., additional, Singh, Harvir, additional, Sirivisoot, Sirinrath, additional, Skuk, Daniel, additional, Soker, Shay, additional, Spector, Myron, additional, Stocum, David L., additional, Strom, Stephen C., additional, Thomson, James A., additional, Tosh, David, additional, Tranquillo, Robert T., additional, Tremblay, Jacques P., additional, Verfaillie, Catherine M., additional, Wang, Zhan, additional, West, Jennifer L., additional, Whittlesey, Kevin J., additional, Williams, Chrysanthi, additional, Williams, David F., additional, Williams, J. Koudy, additional, Witten, Celia, additional, Woo, Savio L.-Y., additional, Wood, Fiona, additional, Yamanaka, Shinya, additional, Yamato, Masayuki, additional, Yazdani, Saami K., additional, Yoo, James J., additional, Yu, Junying, additional, and Zhong, Bonan, additional

Published
2011
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