Plotkin Lab

Led by Lilian Plotkin, PhD, the Plotkin Lab focuses on the role of connexins in the transduction of signals induced by hormonal, pharmacotherapeutic and mechanical stimuli in osteoblasts and osteocytes. For this, the laboratory utilizes in vitro techniques including tissue culture, analysis of protein expression by Western blotting and of gene expression by real time PCR. In addition, ex vivo cultures of bone cells isolated from mice treated with pharmacologic and hormonal agents, and from genetically modified mice are performed. Lastly, genetically modified mice have been generated and their bone phenotype is characterized using in vivo and ex vivo imaging, gene expression techniques and histomorphometric analysis.

As a result of this work, the laboratory has demonstrated that bisphosphonates, agents widely used to treat osteoporosis, prevent osteocyte and osteoblast apoptosis via a novel mechanism that involves opening of connexin43 hemichannel and activation of intracellular signaling molecules. The lab has unveiled a new role of connexin43 on the maintenance of osteocyte viability and in the composition of the bone matrix. Moreover, it has linked for the first time changes on the molecular composition of the cells in bone with cell death and deficient material properties. More recently, the laboratory has begun exploring the interaction between the brain and bone, by testing the consequences of neurological diseases, including epilepsy and fragile X syndrome, in the skeleton using mouse and rat models.

Active Research

Osteocyte apoptosis and regulation of bone resorption with aging

The objective of this application is to investigate the molecular mechanisms by which increased osteocyte apoptosis in Cx43-deficient and old mice results in targeted bone resorption. Plotkin Principal Investigator, R01- AR067210, NIH/NIAMS, 04/01/15-03/31/20

Bone defects in FMR1 deficient mice, a model of autism.

The purpose of this study is to characterize the basis for the reduced bone mass observed in mice lacking FRM1, the gene responsible for fragile X syndrome. Plotkin, Principal Investigator, IUPUI Office of the Vice Chancellor for Research – Research Support Funds Grant, 02/01/17-01/31/18

Research Funding

NIH Diversity Postdocotoral Supplement Award to Alexandra Aguilar-Perez, 04/01/17-03/31/20
Graduate Training Fellowship (T32-AR065971) to Hannah M. Davis, 02/01/17-01/31/19

Recent Publications

Davis HM, Pacheco-Costa R, Atkinson EG, Brun LR, Gortazar AR, Harris J, Hiasa M, Bolarinwa SA, Yoneda T, Ivan M, Bruzzaniti A, Bellido T, Plotkin LI. Disruption of the Cx43/miR21 pathway leads to osteocyte apoptosis and increased osteoclastogenesis with aging. Aging Cell doi: 10.1111/acel.12586, 2017.

Hammond MA, Bernam AG, Pacheco-Costa R, Davis HM, Plotkin LI, Wallace JM. Removing or truncating connexin 43 in murine osteocytes alters cortical geometry, nanoscale morphology, and tissue mechanics in the tibia. Bone 88:85-91, 2016.

Plotkin LI, Gortazar AR, Davis HM, Condon KW, Gabilondo H, Maycas M, Allen MR, Bellido T. Inhibition of osteocyte apoptosis prevents the increase in osteocytic RANKL but it does not stop bone resorption or the loss of bone induced by unloading. Journal of Biological Chemistry. 290:18934-18942, 2015.

Pacheco-Costa R, Davis HM, Sorenson C, Hon MC, Hassan I, Reginato RD, Allen MR, Bellido T, Plotkin LI. Defective cancellous bone structure and abnormal response to PTH in cortical bone of mice lacking Cx43 cytoplasmic C-terminus domain. Bone 81:632-643, 2015.

Pacheco-Costa R, Hassan I, Reginato RD, Davis HM, Bruzzaniti A, Allen MR, Plotkin LI. High Bone Mass in Mice Lacking Cx37 Due to Defective Osteoclast Differentiation. Journal of Biological Chemistry 289:8508-8520, 2014.

Bivi N, Pacheco-Costa R, Brun LR, Murphy TR, Farlow NR, Robling AG, Bellido T, Plotkin LI. Deletion of Cx43 selectively from osteocytes increases the osteogenic response to ulna loading in mice. Journal of Orthopaedic Research 31:1075-1081, 2013.

Bivi N, Nelson M, Faillace M, Li J, Miller LM, Plotkin LI. Deletion of Cx43 from osteocytes results in defective bone material properties and decreased strength in cortical bone. Calcified Tissue International 91:215-224, 2012.

Bivi N, Lezcano V, Romanello M, Bellido T, Plotkin LI. Connexin43 interacts with βarrestin: a pre-requisite for osteoblast survival induced by parathyroid hormone. Journal of Cellular Biochemistry 112:2920-2930, 2011. Featured as “Not to be missed” in IBMS BoneKEy 2011 Jul 1 doi:10.1138/20110518.

Bivi N, Condon K, Allen MR, Farlow N, Passeri G, Rhee Y, Bellido T, Plotkin LI. Cell autonomous requirement of connexin 43 for osteocyte survival: consequences for endocortical resorption and periosteal bone formation. Journal of Bone and Mineral Research 27:374-389, 2012. Featured as “Not to be missed” in IBMS BoneKEy 2011 Nov 1 doi:10.1138/20110538.

Lilian I. Plotkin, PhD

Lilian I. Plotkin, PhD

Associate Professor of Anatomy & Cell Biology
Alexandra Aguilar-Perez, PhD

Alexandra Aguilar-Perez, PhD

Research Fellowship

Addtional Research Team Members

Other research team members include Hannah M. Davis (Graduate Student) and Padmini Deosthale, MS
(Research Technician).