Sudha Agarwal, PhD
Northeastern University, Boston, 1973, Biology (Cell Physiol)
The focus of my lab is in the areas of mechanobiology/bioengineering of cartilage and bone. Briefly, we are involved in the fundamental research and translational studies through:
- Comprehensive understanding of the mechanotransduction pathways at the cellular and subcellular level, that are involved in enhancing repair and regeneration of diseased and healthy cartilage and bone.
- Identification of molecules involved in the tissue responses to mechanical forces and translate these findings for the treatment of joint/bone disorders.
- Development of non-invasive methods to treat joints afflicted with arthritic diseases.
- Application of quantitatively optimal mechanical signals and mediators involved in mechanosignaling to repair cartilage and bone following thorough understanding of the effects of mechanical forces on the cartilage and bone.
For centuries, exercise is known to promote health. Only recently it is becoming clear that mechanical forces control a highly concerted series of biochemical events that direct many homeostatic functions of the body. This mechanoresponsiveness is especially striking in joints, where mechanical loading elicits reparative and regenerative effects. Despite this well accepted phenomenon, how exercise drives mechanoactivated joint repair is little understood. Recently, we have provided evidence that mechanical forces of physiological magnitudes are potent anti-inflammatory and reparative signals in chondrocytes and osteoblasts as well as in cartilage and bone. These signals suppress proinflammatory gene induction by inhibiting NF-?B signaling cascade via TAK1, a kinase upstream of signalosome that controls NF-?B nuclear translocation. Furthermore, mechanical signals act as potent regenerative signals and induce matrix synthesis via induction of transcription factors like Sox-9 in the cartilage and Runx-2 in the bone. We are now extending these studies to examine the signal transduction pathways that are important in tissue regeneration as well as curbing the inflammation, i.e., Wnt/beta-catenin, SMAD, and Akt signaling cascades.
On the other hand, the ongoing studies have demonstrated that exercise induces factors critical in bone remodeling. Our longterm goal is to understand their mechanisms of actions and take these basic science findings to the clinic via translational studies through collaborations with physicians, bioengineers and scientists. With the advancements of technologies for tissue repair and tissue engineering, identification of the molecules that enhance tissue's ability to self-regenerate are quite important. These molecules once delineated can then be applied in an effective manner to augment regenerative capacity of diseased and aging cartilage, as well as allow better integration of tissue engineered transplants, to repair bone afflicted with arthritic diseases.
Impact of lesion location on the progression of osteoarthritis in a rat knee model. Knapik, D. M., Harrison, R. K., Siston, R. A., Agarwal, S. & Flanigan, D. C. Jan 1 2015 In : Journal of Orthopaedic Research. 33, 2, p. 237-245 9 p.
Mechanosignaling in bone health, trauma and inflammation. Knapik, D. M., Perera, P., Nam, J., Blazek, A. D., Rath, B., Leblebicioglu, B., Das, H., Wu, L. C., Hewett, T. E., Agarwal, S. K., Robling, A. G., Flanigan, D. C., Lee, B. S. & Agarwal, S. Feb 20 2014 In : Antioxidants and Redox Signaling. 20, 6, p. 970-985 16 p.
A mechatronic system for quantitative application and assessment of massage-like actions in small animals. Wang, Q., Zeng, H., Best, T. M., Haas, C., Heffner, N. T., Agarwal, S. & Zhao, Y. Jan 1 2014 In : Annals of Biomedical Engineering. 42, 1, p. 36-49 14 p.
The basic science of continuous passive motion in promoting knee health: A systematic review of studies in a rabbit model. Knapik, D. M., Harris, J. D., Pangrazzi, G., Griesser, M. J., Siston, R. A., Agarwal, S. & Flanigan, D. C. Oct 1 2013 In : Arthroscopy - Journal of Arthroscopic and Related Surgery. 29, 10, p. 1722-1731 10 p.
Determinants of alveolar ridge preservation differ by anatomic location. Leblebicioglu, B., Salas, M., Ort, Y., Johnson, A., Yildiz, V. O., Kim, D. G., Agarwal, S. & Tatakis, D. N. Apr 1 2013 In : Journal of Clinical Periodontology. 40, 4, p. 387-395 9 p.
Dynamic regulation of bone morphogenetic proteins in engineered osteochondral constructs by biomechanical stimulation. Nam, J., Perera, P., Rath, B. & Agarwal, S. Mar 1 2013 In : Tissue Engineering - Part A. 19, 5-6, p. 783-792 10 p.
Human umbilical cord blood-derived CD34+ cells reverse osteoporosis in NOD/SCID mice by altering osteoblastic and osteoclastic activities. Aggarwal, R., Lu, J., Kanji, S., Joseph, M., Das, M., Noble, G. J., McMichael, B. K., Agarwal, S., Hart, R. T., Sun, Z., Lee, B. S., Rosol, T. J., Jackson, R., Mao, H. Q., Pompili, V. J. & Das, H. Jun 18 2012 In : PLoS ONE. 7, 6, e39365
Kruppel-like factor 2 (KLF2) regulates monocyte differentiation and functions in mBSA and IL-1β-induced arthritis. Das, M., Lu, J., Joseph, M., Aggarwal, R., Kanji, S., McMichael, B. K., Lee, B. S., Agarwal, S., Ray-Chaudhury, A., Iwenofu, O. H., Kuppusamy, P., Pompili, V. J., Jain, M. K. & Das, H. Feb 1 2012 In : Current Molecular Medicine. 12, 2, p. 113-125 13 p.
Sequential alterations in catabolic and anabolic gene expression parallel pathological changes during progression of monoiodoacetate-induced arthritis. Nam, J., Perera, P., Liu, J., Rath, B., Deschner, J., Gassner, R., Butterfield, T. A. & Agarwal, S. Sep 13 2011 In : PLoS ONE. 6, 9, e24320
Transcriptome-wide gene regulation by gentle treadmill walking during the progression of monoiodoacetate-induced arthritis. Nam, J., Perera, P., Liu, J., Wu, L. C., Rath, B., Butterfield, T. A. & Agarwal, S. Jun 1 2011 In : Arthritis and Rheumatism. 63, 6, p. 1613-1625 13 p.
Biomechanical forces exert anabolic effects on osteoblasts by activation of SMAD 1/5/8 through type 1 BMP receptor. Rath, B., Rath, B., Deschner, J., Schaumburger, J., Tingart, M., Grässel, S., Grifka, J. & Agarwal, S. May 2 2011 In : Biorheology. 48, 1, p. 37-48 12 p.
Modulation of embryonic mesenchymal progenitor cell differentiation via control over pure mechanical modulus in electrospun nanofibers. Nam, J., Johnson, J., Lannutti, J. J. & Agarwal, S. Apr 1 2011 In : Acta Biomaterialia. 7, 4, p. 1516-1524 9 p.
The large zinc finger protein ZAS3 is a critical modulator of osteoclastogenesis. Liu, S., Madiai, F., Hackshaw, K. V., Allen, C. E., Carl, J., Huschart, E., Karanfilov, C., Litsky, A., Hickey, C. J., Marcucci, G., Huja, S., Agarwal, S., Yu, J., Caligiuri, M. A. & Wu, L. C. Mar 10 2011 In : PLoS ONE. 6, 3, e17161
Mechanical signals activate vascular endothelial growth factor receptor-2 to upregulate endothelial cell proliferation during inflammation. Liu, J. & Agarwal, S. Jul 15 2010 In : Journal of Immunology. 185, 2, p. 1215-1221 7 p.
Mechanical signals control SOX-9, VEGF, and c-Myc expression and cell proliferation during inflammation via integrin-linked kinase, B-Raf, and ERK1/2-dependent signaling in articular chondrocytes. Perera, P. M., Wypasek, E., Madhavan, S., Rath-Deschner, B., Liu, J., Nam, J., Rath, B., Huang, Y., Deschner, J., Piesco, N., Wu, C. & Agarwal, S. May 28 2010 In : Arthritis Research and Therapy. 12, 3, R106