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.

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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

R01- AR067210, NIH/NIAMS, 04/01/15-03/31/20
Graduate Training Fellowship (T32-AR065971) to Alyson L. Essex (co-directed with Andrea Bonetto, PhD), 09/01/19-08/31/21\
Cagiantas Scholarship from the Indiana University School of Medicine to Hannah M. Davis, 09/01/18-08/31/19

Recent Publications

Plotkin LI, Davis HM, Essex AL. RAGE signaling in musculoskeletal biology. Skeletal Biology and Regulation Section in Current Osteoporosis Reports section, Current Osteoporosis Reports (M Forwood and A Robling, Section Editors, D Burr, Editor in Chief) doi: 10.1007/s11914-019-00499-w, in press, 2019.

Bullock WA, Plotkin LI, Robling AG, Pavalko FM. Mechanotransduction in bone formation/maintenance. In Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 9th Edition, (J. Bilezikian, editor), Wiley Blackwell, 75-83, 2019.

Bellido T, Plotkin LI, Bruzzaniti A. Bone Cells. In Basic and Applied Bone Biology (D.B. Burr and Allen MR, editors), Elsevier, in press, 2019.

Plotkin LI, Aguilar-Perez A, Bivi N. Local regulation of bone cell function. In Basic and Applied Bone Biology (D.B. Burr and Allen MR, editors), Elsevier, in press, 2019.

Plotkin LI, Davis, HM. Role of connexins and pannexins in bone and muscle mass and function. In Osteosarcopenia – Translational Research in Bone, Muscle and Fat Interactions (G. Luque, editor), Springer, in press, 2019.

Plotkin LI, Bruzzaniti A. Molecular signaling in bone cells: regulation cell differentiation and survival. In Advances in Protein Chemistry and Structural Biology – Intracellular signaling proteins (R. Donev, Editor). Elsevier, in press, 2019.

Lilian I. Plotkin, PhD

Assistant Dean for Faculty Affairs and Professional Development

Additional Research Team Members

Other research team members include Hannah M. Davis (graduate student) and Padmini Deosthale, MS (research technician).