I am currently a Staff Scientist I in the Rosen Lab. My interests in bone development and its role in regulating whole body metabolism began during my doctoral training and have continued in the Rosen laboratory. I am involved in a number of different projects which I have described briefly below.
Role of Nocturnin in Bone
Nocturnin (Noc) is a circadian regulated deadenylase. We found that the loss of Nocturnin is protective of bone loss during Rosiglitazone therapy. This work could have major translational implications since the thiazolidinediones remain a widely used treatment for Type 2 diabetes mellitus. In course of my experiments with Nocturnin I identified a potential mitochondrial target sequence in this protein. Functional studies are ongoing to further characterize this protein using Dox inducible overexpression models. (Manuscript in preparation with Phuong Le and Sheila Bornstein)
Fig1: Shows representative 3D images of cortical and trabecular bone (femurs) of control (saccharin) and Nocturnin overexpression (Saccharin+Dox) mice using microCT analysis.
Bioenergetics of osteogenesis
Based on my observations during the Nocturnin experiments, I started studying the role of mitochondrial respiration during osteoblast differentiation. To this end, I have extensively used the SeaHorse XF24 Analyzer (www.mmcri.org). I have used both primary calvarial cells and preosteoblasts MC3T3E1 cells to study this as shown in Fig 2. The results from the calvarial osteoblast study using the SeaHorse XF24Analyzer have led us to propose studies to delineate the metabolic pathways that are active in osteoblasts. Furthermore, I have studied the metabolic pathways that are active in 3T3L1 and Ear mesenchymal cells during adipogenesis using the Seahorse XF24 analyzer. The goal is to identify if the bioenergetic pathways in adipocytes are different from the osteoblast metabolic pathways during differentiation.
Fig2: Shows Oxygen consumption rates for Nondifferentiated (red) osteoblasts and differentiated (blue) osteoblasts in the left panel and extracellular acidification rates in the right hand panel using the XF24 analyzer.
IRS1 and osteoblast respiration
Insulin Receptor substrate1 (IRS1) is a signaling molecule that is downstream of IGF1 signaling. Our lab has an IRS1 null spontaneous mouse model. Mice harboring this mutation are lean and have defects in adipose tissue along with reduced cortical bone and bone lengths. We have exploited this defect to study the role of IGF1 signaling in osteoblast and adipocytes respiration. This is a collaborative project with Dr’s Martin Brand and Akos Gerencser (Buck Institute of Aging) and Dr. David Clemmons (at the University of North Carolina). (Manuscript in preparation with Victoria DeMambro, two photon microscopy Dr. Akos Gerencser at Buck Institute)
Fig3: Two photon microscopy image showing collagen in white (ex vivo calvariae) and alkaline phosphatase positive cells in green.
Kapadia RM, Guntur AR
, Reinhold MI, Naski, MC. Glycogen synthase kinase 3 controls endochondral bone development: contribution of fibroblast growth factor 18. Dev Biol. 2005; Sep 15;285(2):496-507.
Guntur AR, Reinhold MI, Cuellar J, Naski MC. Conditional ablation of Pten in osteoprogenitors stimulates FGF signaling. Development. 2011; Apr;138(7); 1433-1444. doi: 10.1242/dev.058016. PMCID: PMC3050668
Guntur AR, Le PT, Farber CR, Rosen CJ. Bioenergetics during calvarial osteoblast differentiation reflects strain differences in bone mass. Endocrinology. 2014;155(5):1589-95. PMCID:PMC3990840.
DeMambro VE, Le PT, Guntur AR, Maridas DE, Canalis E, Nagano K, Baron R, Clemmons DR, Rosen CJ. Igfbp2 Deletion in Ovariectomized Mice Enhances Energy Expenditure but Accelerates Bone Loss. Endocrinology. 2015;156(11):4129-40. Epub 2015/08/01. doi: 10.1210/en.2014-1452. PubMed PMID: 26230658; PMCID: Pmc4606757.
Member, American Society for Bone and Mineral Research
Peer reviewer for the following journals:
- Mechanisms of Aging and Development
- International Journal of Oral Science
- Stem cell research
- International Immunopharmacology
- Journal of bone and mineral research