Nicola Partridge
Professor

UMDNJ-RWJMS
Dept. of Physiology/Biophysics
Piscataway. NJ 08854
(732) 235-4552
FAX - 5038
partrinc@umdnj.edu


Signal transduction. molecular endocrinology. transcriptional regulation. metalloproteinases

We have shown that parathyroid hormone (PTH) induces the transcription of collagenase-3 (matrix metalloproteinase-13) in osteoblastic cells. This involves the protein kinase A pathway and induction of activator protein-1 transcription factors as well as phosphorylation of another transcription factor. Runx 2. Thus. PTH regulates both transcription factors through this pathway. either by increasing their expression or altering their phosphorylation. We have also shown that the proteins interact physically in a nucleosomal structure. recruiting other proteins such as co-activators and modifiers of the nucleosome. In another project. we are investigating the signal transduction pathways whereby PTH induces anabolic effects on bone and determining novel genes regulated by this hormone. In one other project we have shown that extracellular concentrations of collagenase-3 are regulated by the existence of a specific receptor which binds the enzyme. Subsequent internalization and degradation of collagenase-3 require transfer to the endocytotic receptor. the low-density lipoprotein receptor-related protein. We are now further characterizing the collagenase-3 removal process in osteoblasts. fibroblasts as well as chondrocytes. The latter work could lead to new treatments for osteoarthritis.

Selected Publications

Raggatt LJ, Qin L, Tamasi J, Jefcoat SC Jr, Shimizu E, Selvamurugan N, Liew FY, Bevelock L, Feyen JH, Partridge NC. (2008) Interleukin-18 is regulated by parathyroid hormone and is required for its bone anabolic actions. J Biol Chem. 283(11):6790-8.

Bergenstock MK, Partridge NC. (2007) Parathyroid hormone stimulation of noncanonical Wnt signaling in bone. Ann N Y Acad Sci.1116:354-9. Review.

Li X, Qin L, Bergenstock M, Bevelock LM, Novack DV, Partridge NC. (2007) Parathyroid hormone stimulates osteoblastic expression of MCP-1 to recruit and increase the fusion of re/osteoclasts. J Biol Chem. 282(45):33098-106.

Li X, Liu H, Qin L, Tamasi J, Bergenstock M, Shapses S, Feyen JH, Notterman DA, Partridge NC. (2007) Determination of dual effects of parathyroid hormone on skeletal gene expression in vivo by microarray and network analysis. J Biol Chem. 282(45):33086-97.

Shimizu E, Selvamurugan N, Westendorf JJ, Partridge NC. (2007) Parathyroid hormone regulates histone deacetylases in osteoblasts. Ann N Y Acad Sci. 1116:349-53.

Zhu J, Jia X, Xiao G, Kang Y, Partridge NC, Qin L. (2007) EGF-like ligands stimulate osteoclastogenesis by regulating expression of osteoclast regulatory factors by osteoblasts: implications for osteolytic bone metastases. J Biol Chem. 282(37):26656-64.

Selvamurugan N, Kwok S, Vasilov A, Jefcoat SC, Partridge NC. (2007) Effects of BMP-2 and pulsed electromagnetic field (PEMF) on rat primary osteoblastic cell proliferation and gene expression. J Orthop Res. 25(9):1213-20.

Partridge NC, Li X, Qin L. (2006) Understanding parathyroid hormone action. Ann N Y Acad Sci. 1068:187-93.

Selvamurugan N. Jefcoat SC. Kwok S. Kowalewski R. Tamasi JA. Partridge NC. (2006) Overexpression of Runx2 directed by the matrix metalloproteinase-13 promoter containing the AP-1 and Runx/RD/Cbfa sites alters bone remodeling in vivo. J Cell Biochem. 99(2):545-57.

Boumah CE. Selvamurugan N. Partridge NC. (2005) Transcription in the osteoblast: regulatory mechanisms utilized by parathyroid hormone and transforming growth factor-beta. Prog Nucleic Acid Res Mol Biol. 80:287-321.

Qin L. Partridge NC. (2005) Stimulation of amphiregulin expression in osteoblastic cells by parathyroid hormone requires the protein kinase A and cAMP response element-binding protein signaling pathway. J Cell Biochem. 96(3):632-40.

Kwok S. Qin L. Partridge NC. Selvamurugan N. (2005) Parathyroid hormone stimulation and PKA signaling of latent transforming growth factor-beta binding protein-1 (LTBP-1) mRNA expression in osteoblastic cells. J Cell Biochem. 95(5):1002-11.

Qin L. Li X. Ko JK. Partridge NC. (2005) Parathyroid hormone uses multiple mechanisms to arrest the cell cycle progression of osteoblastic cells from G1 to S phase. J Biol Chem. 280(4):3104-11.

Qin L. Tamasi J. Raggatt L. Li X. Feyen JH. Lee DC. Dicicco-Bloom E. Partridge NC. (2005) Amphiregulin is a novel growth factor involved in normal bone development and in the cellular response to parathyroid hormone stimulation. J Biol Chem. 280(5):3974-81.

Selvamurugan N. Kwok S. Partridge NC. (2004) Smad3 interacts with JunB and Cbfa1/Runx2 for transforming growth factor-beta1-stimulated collagenase-3 expression in human breast cancer cells. J Biol Chem. 279(26):27764-73.

Qin L. Raggatt LJ. Partridge NC. (2004) Parathyroid hormone: a double-edged sword for bone metabolism. Trends Endocrinol Metab. 15(2):60-5.

Shah R. Alvarez M. Jones DR. Torrungruang K. Watt AJ. Selvamurugan N. Partridge NC. Quinn CO. Pavalko FM. Rhodes SJ. Bidwell JP. (2004) Nmp4/CIZ regulation of matrix metalloproteinase 13 (MMP-13) response to parathyroid hormone in osteoblasts. Am J Physiol Endocrinol Metab. 287(2):E289-96.

Selvamurugan N. Kwok S. Alliston T. Reiss M. Partridge NC. (2004) Transforming growth factor-beta 1 regulation of collagenase-3 expression in osteoblastic cells by cross-talk between the Smad and MAPK signaling pathways and their components. Smad2 and Runx2. J Biol Chem. 279(18):19327-34.

Qin. L.. Qiu. P.. Wang. L.. Li. X.. Swarthout. J.T.. Soteropoulos P.. Tolias. P. and Partridge. N.C. (2003). Gene expression profiles and transcription factors involved in parathyroid hormone signaling in osteoblasts revealed by microarray and bioinformatics. J. Biol. Chem. 278:19723-19731.

Walling. H.W.. Raggatt. L.J.. Irvine. D.W.. Barmina. O.Y.. Toledano. J.E.. Goldring. M.B.. Hruska. K.A.. Adkisson. H.D.. Burdge. R.E.. Gatt. C.J.. Jr.. Harwood. D.A. and Partridge. N.C. (2003). Impairment of the collagenase-3 endocytotic receptor system in cells from patients with osteoarthritis. Osteoarthritis and Cartilage 11:854-863.

Swarthout. J.T.. Tyson. D.R.. Jefcoat. S.C. and Partridge. N.C. (2002). Induction of transcriptional activity of the cAMP response element binding protein by parathyroid hormone and epidermal growth factor in osteoblastic cells. J. Bone Min. Res. 17:1401-1407.

D'Alonzo. R.C.. Kowalski. A.J.. Denhardt. D.T.. Nickols. G.A.. and Partridge. N.C. (2002). Regulation of collagenase-3 and osteocalcin gene expression by collagen and osteopontin in differentiating MC3T3-E1 cells. J. Biol. Chem. 277:24788-24798.

Raggatt. L.J. and Partridge. N.C. (2002). HMG-CoA reductase inhibitors as immunomodulators: Potential use in transplant rejection. Drugs 62:2185-2191.

Selvamurugan. N.. Fung. Z. and Partridge. N.C. (2002). Transcriptional activation of collagenase-3 by transforming growth factor-b1 is via MAPK and Smad pathways in human breast cancer cells. FEBS Lett. 532:31-35.

Qin. L.. Qiu. P.. Wang. L.. Li. X.. Swarthout. J.T.. Soteropoulos P.. Tolias. P. and Partridge. N.C. (2003). Gene expression profiles and transcription factors involved in parathyroid hormone signaling in osteoblasts revealed by microarray and bioinformatics. J. Biol. Chem. 278:19723-19731.

Walling. H.W.. Raggatt. L.J.. Irvine. D.W.. Barmina. O.Y.. Toledano. J.E.. Goldring. M.B.. Hruska. K.A.. Adkisson. H.D.. Burdge. R.E.. Gatt. C.J.. Jr.. Harwood. D.A. and Partridge. N.C. (2003). Impairment of the collagenase-3 endocytotic receptor system in cells from patients with osteoarthritis. Osteoarthritis and Cartilage 11:854-863.