Bone cell biology and medicine
Bone is a metabolically active and highly organised tissue that needs continuous remodeling. Bone contains two distinct cell types, the osteoblasts, essential for bone formation (synthesis); and the osteoclasts, essential for bone resorption (break down). Co-ordinated activity of osteoblasts and osteoclasts is essential to maintain the bone homeostasis and structural integrity of the skeleton. An imbalance of osteoblast and osteoclast functions can result in skeletal abnormalities characterized by increased or decreased bone mass. Increased osteoclast activity is a major cause of bone loss in osteoporosis, rheumatoid arthritis, and bone metastasis. Also, osteoblast number is decreased in osteoporosis. Therefore, to develop the therapy for these diseases it is important to know the regulation of bone remodeling at cellular and molecular level. My team is investigating the role of interleukins in regulation of osteoclasts and osteoblast differentiation and their function. Following are some of the research leads we have obtained. Importantly, we investigated that Interleukin-3 (IL-3), plays an important role in prevention of bone loss and stimulation of new bone formation. Following research leads we have obtained.
We revealed for the first time that recombinant mouse IL-3 acts directly on mouse osteoclast precursors, and inhibits RANKL (a osteoclast differentiation factor)-induced osteoclast differentiation. We investigated that IL-3 inhibits osteoclast differentiation by preventing RANKL-induced activation of NF-kB (Khapli et al. 2003, The Journal of Immunology 171:142-151).
TNF-a is crucial to the pathogenesis of osteoporosis, and bone and joint destructions in rheumatoid arthritis. Further, we found that IL-3 also inhibits TNF-a-induced osteoclast differentiation in mouse osteoclast precursors and inhibits surface expression of both c-Fms and TNF receptors 1 and 2 (Yogesha et al., 2005, Journal of Biological Chemistry 280:11759-11769).
IL-3 inhibits TNF-a-induced bone resorption in presence of other proinflammatory cytokines such as IL-1a, TGF-b1, TGF-b3, IL-6 and PGE2. IL-3 prevented TNF-a-induced c-fos nuclear translocation, and AP-1 activation. Interestingly, IL-3 prevents the development of inflammatory arthritis in mice, and protects cartilage and bone destruction [Yogesha et al, 2008, The Journal of Immunology 182: 361-370). These studies in mice suggest the therapeutic importance of IL-3 in prevention of pathological bone loss.
This study was further extended to human osteoclast differentiation and bone resorption. Interestingly, recombinant human IL-3 also inhibits human osteoclast differentiation and bone resorption. Moreover, human IL-3 inhibits bone resorption in osteoclast precursors isolated from osteoporotic individuals (Gupta et al., 2010 The Journal of Immunology 185:2261-2272).
We developed mouse model of human rheumatoid arthritis and demonstrated that IL-3 attenuates collagen-induced arthritis by modulating the development of regulatory T cells (Srivastava et al., The Journal of Immunology. 2011, 186:2262-2272).
In osteoporosis osteoblast number is decreased. Therefore, the regenerative potential of bone is poor in osteoporosis. In further investigations we found that IL-3 increases osteoblast differentiation and bone mineralization from human mesenchymal stem cells in both in vitro and in vivo conditions (Barhanpurkar et al. under review).
These investigations and leads obtained by us suggest that IL-3 has a potential to inhibit bone loss and also to induce new bone formation. Thus, IL-3 may have therapeutic potential for the treatment of human osteoporosis, inflammatory arthritis and other important diseases of clinical importance.
In another study, we have identified some novel molecule from marine organism Indian Green Mussel Perna Viridis that inhibits osteoclastogenesis and bone resorption in vitro and in vivo (US Patent # 6,905,710, Granted on June 14, 2005). The structure of the new molecule is also identified (US Patent # 7,335,686, Granted on February 26, 2008).
Ph.D. (Medicine) University of London, England
Recipient of Commonwealth Fellowship Award.
M.V.Sc. (Surgery) Post Graduate Institute, PKV, Akola(M.S.),
Distinction and First Rank in the University.
B.V.Sc. Nagpur Veterinary College, Nagpur.
First Class, Recipient of Merit Scholarship.
Field of Specialization
Bone and cartilage cell biology and medicine, osteoimmunology, arthritis, stem cell science and regenerative medicine.
Manasa G. Garimella, Supinder Kour, Vikrant Piprode, Monika Mittal, Anil Kumar, Lekah Rani, Satish T. Pote, G. Mishra, Naibedya Chattopadhyay and Mohan R. Wani (2015). Adipose-derived mesenchymal stem cells prevent systemic bone loss in collagen-induced arthritis. The Journal of Immunology (In press).
T. Ahmad, S. Mukherjee, B. Pattnaik, M. Kumar, S. Singh, M. Kumar, R. Rehman, B. K. Tiwari, K. A. Jha, Amruta P. Barhanpurkar, Mohan R. Wani, S. S, Roy, U. Mabalirajan, Balram Ghosh and Anurag Agrawal (2014) Miro1 regulates intercellular mitochondrial transport and enhances mesenchymal stem cell rescue efficacy. EMBO J. 33:994-1010.
Parmanand Malvi, Vikrant Piprode, B. Chaube, S. T. Pote, M. Mittal, N. Chattopadhyay, Mohan R. Wani and Bhat MK (2014) High fat diet promote achievement of peak bone mass in young rats. Biochem Biophys Res Commun. 455:133-138.
Shitu Jindal, Rajesh Bansal, B. P. Singh, Rajiv Pandey, TSN ShankarNarayanan, Mohan R. Wani and Vakil Singh (2014) Enhanced osteoblast proliferation and corrosion resistance of commercially pure titanium through surface nanostructuring by ultrasonic shot peening and stress relieving. J Oral Implantol. 40:347-55.
Archana Singh, B P Singh, Mohan R. Wani, Dinesh Kumar, J. K. Singh and Vakil Singh (2013) Effect of anodization on corrosion behaviour and biocompatibility of Cp-titanium in simulated body fluid. Bull. Mater. 36(5):931–937.
Amruta P Barhanpurkar, Navita Gupta, Rupesh K. Srivastava, Geetanjali B. Tomar, Sameer P. Naik, Snehal R. Joshi, Satish T. Pote, Gyan C. Mishra and Mohan R. Wani (2012). IL-3 promotes osteoblast differentiation and bone formation in human mesenchymal stem cells. Biochem Biophys Res Commun. 418:669-75.
Rupesh K. Srivastava, Geetanjali B. Tomar, Amruta P Barhanpurkar, Navita Gupta, Satish T. Pote, Gyan C. Mishra and Mohan R. Wani (2011). IL-3 attenuates collagen-induced arthritis by modulating the development of Foxp3+ regulatory T cells. The Journal of Immunology 186:2262-2272.
R. Raju, L. Balakrishnan, V. Nanjappa, M. Bhattacharjee, D. Genet, B. Muthusamy, J. K. Thomas, J. Sharma, B. A. Rahiman, H. C. Harsha, S. Shankar, T.S.K. Prasad, S. S. Mohan, G. D. Bader, M. R. Wani, and A. Pandey. A comprehensive manually curated reaction map of RANKL/RANK signaling pathway. Database (Oxford). In press.
Shruti M. Khapli, Geetanjali B. Tomar, Amruta P. Barhanpurkar, Navita Gupta, S. D. Yogesha, Satish T. Pote and Mohan R. Wani (2010) Irreversible inhibition of RANK expression as a possible mechanism for IL-3 inhibition of RANKL-induced osteoclastogenesis. Biochem. Biophys. Res. Commun. 399: 688-693.
Navita Gupta, Amruta P Barhanpurkar, Geetanjali B. Tomar, Rupesh K. Srivastava, Satish T. Pote, Gyan C. Mishra and Mohan R. Wani (2010). IL-3 inhibits human osteoclastogenesis and bone resorption through down-regulation of c-Fms, and diverts the cells to dendritic cell lineage. The Journal of Immunology 185:2261-2272.
Hiral M. Jhaveri, Mahesh S. Chavan, Geetanjali B. Tomar, Vijay L. Deshmukh, Mohan R. Wani and Preston D. Miller Jr. (2010). Acellular dermal matrix seeded with autologous gingival fibroblasts for the treatment of gingival recession: A proof-of-concept study. J Periodontol. 81:616-625.
Geetanjali B. Tomar, Rupesh K. Srivastava, Navita Gupta, Amruta P Barhanpurkar, Satish T. Pote, Hiral M. Jhaveri, Gyan C. Mishra and Mohan R. Wani (2010). Human gingiva-derived mesenchymal stem cells are superior to bone marrow-derived mesenchymal stem cells for cell therapy in regenerative medicine. Biochem. Biophys. Res. Commun. 393: 377-383.
S. D. Yogesha, Shruti M. Khapli, Rupesh K. Srivastava, Latha S. Mangashetti, Satish T. Pote, Gyan C. Mishra and Mohan R. Wani (2009). IL-3 prevents inflammatory arthritis. In Research Highlight Section. Nature Reviews Rheumatology 5:180.
S. D. Yogesha, Shruti M. Khapli, Rupesh K. Srivastava, Latha S. Mangashetti, Satish T. Pote, Gyan C. Mishra and Mohan R. Wani (2008). IL-3 Inhibits TNF-a-Induced Bone Resorption, and Prevents Inflammatory Arthritis. The Journal of Immunology 182: 361-370.
Mohan R. Wani (2007).Bone remodeling by osteoclasts and osteoblasts. Cell Biology Newsletter 27:3-7 (Invited General Review Article for Indian students and scientists).
Latha S. Mangashetti, Shruti M. Khapli, and Mohan R. Wani (2005). IL-4 inhibits bone-resorbing activity of mature osteoclasts by affecting NF-kB and Ca2+ signaling. The Journal of Immunology 175:917-925.
Yogesha, S. D., Shruti M. Khapli, and Mohan R. Wani (2005). Interleukin-3 and granulocyte-macrophage colony-stimulating factor inhibits (TNF)-a-induced osteoclast differentiation by down-regulation of expression of TNF receptors 1 and 2. Journal of Biological Chemistry 280:11759-11769.
Shruti M. Khapli, Latha S. Mangashetti, Yogesha S.D. and Mohan R. Wani (2003) IL-3 acts directly on osteoclast precursors and irreversibly inhibits receptor activator of NF-kB ligand-induced osteoclast differentiation by diverting the cells to macrophage lineage. The Journal of Immunology 171:142-151.
Lean, J. M., Matsuo, K., Fox, S. W., Fuller, K., Gibson, F. M., Draycott, G., Wani, M. R., Bayley, K. E., Wong, B., Choi, Y., Wagner, E. F. and Chambers, T. J. (2000). Osteoclast lineage commitment of bone marrow precursors through expression of membrane-bound TRANCE. Bone 27(1) 29-40.
Fuller, K., Lean, J. M., Wani, M. R. and Chambers, T. J. (2000). A role for TGFb in osteoclast differentiation and activation. Journal of Cell Science 113(13) 2445-2453.
Wani, M. R., Fuller, K., Kim, N.S., Choi, Y. and Chambers, T. (1999). Prostaglandin E2 co-operates with TRANCE in osteoclast induction from hemopoietic precursors: Synergistic activation of differentiation, cell spreading and fusion. Endocrinology 140(4)1927-1935.
Wani, M.R., Bayley, K. E., Fuller, K. and Chambers, T. J. (1999). Residronate suppresses osteoclast differentiation and function through an effect on the osteoclast lineage that can be reversed by mevalonic acid. Journal of Bone and Mineral Research 14 (S1) 219.
Wani, M.R. and Kulkarni, P.E. (1996). Prepucial sarcoid in a horse. Ind. J. Vet. Surg. 17(1) 56-56.
Wani, M.R. and Kulkarni, P.E. (1995). Evaluation of autogenous free full thickness, split thickness and pinch skin grafts in dogs. Ind. J. Vet. Surg. 16(2) 107-110.
Wani, M.R. and Kulkarni, P.E. (1995). Harvesting of free skin grafts in dogs. Ind. J. Vet. Surg. 16(2) 125-126.
Gokhale, B. B; Tawade, Y.V., Bharatia, P.R., Parakh, A.P. Mojamdar, M., Bhonde, R.R. and Wani, M.R. (1991). Use of organ cultured foetal skin as allograft in treatment of resistant vitiligo. Ind. J. Dermatology, Venerology, Leprology 57:272-275.
Wani, M. R; Parab, P. B; Chatterji, A (2003). Pharmaceutical composition useful for inhibition of osteoclast formation and a process for the extraction of mussel hudrolysate from Indian green mussel. US Patent # 6,905,710 (Granted on June 14, 2005).
Rao, K. V. S; Wani, M. R; Manivel, V. S; Parameswaran P; Singh, V. K; Anand, R. V; Desa, E; Mishra, G. C; Chatterji, A (2005). Method and composition for treating osteoporosis. US Patent # 7,335,686 (Granted on February 26, 2008)
Rao, K. V. S; Wani, M. R; Manivel, V. S; Parameswaran P; Singh, V. K; Anand, R. V; Desa, E; Mishra, G. C; Chatterji, A. Novel molecules to develop drug for the treatment of osteoporosis (Patent filed 0412NF2003 India, 10/747,671 US, PCT/INO3/00431).
Awards and Achievements
Fellow, National Academy of Sciences (FNASc)
"National Bioscience Award for Career Development 2009" for outstanding research contributions in the field of Bone Remodeling and Medicine by Department of Biotechnology, Govt. of India, New Delhi.
"B. M. Birla Science Prize 2004" for outstanding research contributions in the field of Bone Cell Biology and Medicine. This award was given by the B. M. Birla Science Centre, Hyderabad.
Prof. B. K. Bachhawat International Award for Young Scientists for the year 2006 by Christian Medical College, Vellore, India.
DBT Overseas Associate-ship Award 2005-2006 by Dept. of Biotechnology, Govt. of India, New Delhi.
Elected Member of Guha Research Conference.
Member, Molecular Immunology Forum.
Chancellor Nominee as Executive Council (Governing Body) Member, Maharashtra Animal and Fisheries Sciences University (MAFSU), Nagpur (current).
Commonwealth Fellowship Award by Association of Commonwealth Universities, England (1996-1999).
Gold Medal for securing Distinction and First Rank in the University in M.V.Sc. degree (1989).
ICAR merit scholarship during BVSc (1982-1986).
Member of International and National Professional Bodies
Life Member, Indian Society of Cell Biology, India.
Member, American Society for Bone and Mineral Research, USA.
Member, International Chinese Hard Tissue Society, China.
Executive Committee Member, Indian Society of Cell Biology for the term April 2007-March 2009.
Life member, Laboratory Animal Association of India.
Member of Academic Bodies
Adjunct Professor, Shivaji University, Kolhapur (current).
Member, Committee for the Purpose of Control and Supervision on Experiments on Animals (CPCSEA) of various organizations including National Institute of Virology, Pune; BAIF, Pune; RajBioteck, Pune; Pune University; and NTRC, Pune (current).
Member, Institutional Bio-safety Committee of BAIF, Pune (current).
Contribution as a Reviewer
Reviewed research papers for National and International Journals, and reviewed many research grant proposals for National (DBT, DST and ICMR) and International (BBSRC and Dutch-Review) funding agencies. Participated in setting up of question papers for DBT? recruitment of medical scientists and PhD students.
Invited talk delivered/Chaired Scientific Sessions : 32
Other administrative responsibilities
President, NCCS Staff Welfare Society.
Scientist in-charge Central Sterilization Facility of NCCS.
Scientist in-charge NCCS Guest-House.
Shruti M. Khapli (PhD completed) Latha S Mangashetti (PhD completed) S. D. Yogesha (PhD completed) Geetanjali Joshi-Tomar (PhD completed) Navita Gupta (PhD completed) Rupesh Srivastava (PhD completed) Amruta barhanpurkar (PhD completed) Hiral M Jhaveri (M.D.S. completed) Christie Aguiar (M.V.Sc. completed) Supinder Kaur (JRF, registered for PhD) Gayatri Manasa (JRF, registered for PhD) Snehal Joshi (JRF, registered for PhD) Vikrant Piprode (JRF, registered for PhD) Kanupriya Singh (JRF, registered for PhD) Satish T Pote, (Lab Technician)