Molecular regulation of bone metabolism
Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku
Kati Tarkkonen, PhD; Vappu Nieminen-Pihala, MSc; Fan Wang, MSc; Jemina Lehto, MSc; Rana Al Majidi, MSc; Petri Rummukainen, BSc; Tero Puolakkainen, DDS
The goal of the project:
The old paradigm of bone as a mere structural element has evolved dramatically in recent years. Bone tissue has now emerged as a dynamic endocrine organ capable of regulating diverse physiologic functions such as hematopoiesis, calcium and phosphate homeostasis as well as energy metabolism. Bone consists of several different cell types, the bone cells (osteoblasts, osteocytes and osteoclasts), the hematopoietic stem cells (HSCs) and their off spring as well as bone marrow adipocytes. The complex interplay between these different cell types within the bone marrow microenvironment is essential for normal bone metabolism and for the regulatory functions of bone tissue. Our research group is interested in the molecular mechanisms of these abundant cellular interactions. Moreover, we focus to unravel the essential signaling pathways that control bone cell differentiation and their mechanisms of action both on the broader chromatin landscape as well as at the promoter level. We are also working to characterize the functions and metabolic roles of bone marrow adipocytes. Ultimately, our goal is to identify novel therapeutic targets for metabolic and malignant bone diseases.
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Lotinun S, Kiviranta R, Matsubara T, Alzate JA, Neff L, Lüth A, Koskivirta I, Kleuser B, Vacher J, Vuorio E, Horne WC, Baron R. Osteoclast-specific cathepsin K deletion stimulates S1P-dependent bone formation. J Clin Invest. 2013 Feb;123(2):666-81.
Kiviranta R, Yamana K, Saito H, Ho DK, Laine J, Tarkkonen K, Nieminen-Pihala V, Hesse E, Correa D, Määttä J, Tessarollo L, Rosen ED, Horne WC, Jenkins NA, Copeland NG, Warming S, Baron R. Coordinated transcriptional regulation of bone homeostasis by Ebf1 and Zfp521 in both mesenchymal and hematopoietic lineages. J Exp Med. 2013 May 6;210(5):969-85.
Kang S, Akerblad P, Kiviranta R, Gupta RK, Kajimura S, Griffin MJ, Min J, Baron R, Rosen ED. Regulation of Early Adipose Commitment by Zfp521. PLOS Biology. 2012 Nov;10(11):e1001433.
Hesse E, Saito H, Kiviranta R, Correa D, Yamana K, Neff L, Toben D, Duda D, Atfi A, Geoffroy V, Horne WC and Baron R. Zfp521 controls bone mass by attenuating Runx2 activity in an HDAC3-dependent manner. J Cell Biol. 2010 Dec 27;191(7):1271-83