Frank Beier


Frank Beier

Canada Research Chair in Musculoskeletal Health
University of Erlangen-Nurnberg
Dip. of Biology University of Erlangen-Nurnberg
Office:  Dental Sciences Building, Room 0035
Phone: (519) 661-2111 ext 85344
Fax: (519) 661-3827
Visit:  Dr. Beier's Homepage
See Publications by Frank Beier on PubMed

Skeletal development is a complex process that involves interactions between multiple cell types and is regulated by numerous genetic and environmental factors. Deregulation of any of these factors can lead to serious pathologies such as various forms of dwarfism (e.g. chondrodysplasias) or skeletal tumors. Moreover, improper skeletal development is directly linked to diseases of the adult skeleton such as osteoarthritis.

The majority of our skeleton - for example the ribs, vertebrae and the bones of our limbs - form through the process of endochondral ossification in which the later bone is first laid down as a cartilage model. The cells of the cartilage, the chondrocytes, control the length, shape and function of endochondral bones. Our lab is interested in the signaling pathways and molecular mechanisms that regulate the biology of chondrocytes and other skeletal cells. In this context, we follow three overlapping areas of research.

One focus of the lab is the role of intracellular signaling pathways in chondrocytes. We have demonstrated important functions for signaling molecules of the Rho GTPase and several kinase families (e.g. MAP, PI3K/AKT, GSK-3) in the control of chondrocyte proliferation and differentiation. Current projects address the function of selected signaling molecules in cartilage in vivo and the elucidation of their mechanisms of action (such as effects on gene expression and cytoskeletal organization). We are especially interested in the interactions of chondrocytes with other cell types, including endothelial and perichondral cells as well as osteoblasts and osteoclasts. We utilize knockout mice, organ and cell cultures coupled to a large variety of molecular and cellular assays in these studies. These studies are funded by the Canadian Institutes of Health Research (CIHR).

A second line of investigation addresses the roles of transcriptional regulators of chondrocyte differentiation. In particular, we are interested in members of the nuclear receptor family, such as glucocorticoid receptor and RORalpha. We are using genetically altered mice in conjunction with microarray analyses and cell biological approaches to identify the roles and target genes of these transcription factors in skeletal development. More recently, we have expanded these studies to explore epigenetic mechanisms involved in cartilage gene expression and to examine of the roles of nuclear receptors in the pathogenesis of osteoarthritis. These studies are also funded by CIHR.

Our third area of interest are the molecular mechanisms involved in the progression of osteoarthritis. Through microarray analyses we have identified several pathways (such as TGFalpha-EGFR signaling) that possible contribute to osteoarthritis. We are now testing the function of some of these pathways using genetic and surgical models of osteoarthritis, together with cell and organ culture and biochemical techniques. In particular, we are testing whether drugs that modulate activity of these pathways present suitable approaches to halt or slow osteoarthritis progression in animal models. These studies are supported by CIHR and the National Institutes of Health (NIH, US).

  • Bush, J.R., and Beier, F. (2013). TGF-beta and osteoarthritis – the good and the bad. Nature Medicine 19, 667-669. [view HTML]
  • Watson, L.A., Solomon, L.A., Li, J., Jiang, Y., Edwards, M., Shin-ya, K., Beier, F., and Bérubé, N.G. (2013). ATRX deficiency induces telomere dysfunction, endocrine defects, and reduced lifespan. J. Clin. Invest. 123, 2049-2063. [view HTML]
  • Vasheghani, F., Monemdjou, R., Fahmi, H., Zhang, Y., Perez, G., Blati, M., St-Arnaud, R., Pelletier, J.-P, Beier, F., Martel-Pelletier, J., and Kapoor, M. (2013). Adult cartilage-specific peroxisome proliferator-activated receptor gamma knockout mice exhibit the spontaneous osteoarthritis phenotype. Am. J. Pathology 182, 1099-1106. [view HTML]
  • Poulet, B., Ulici, V., Stone, T.,C. Pead, M., Gburcik, V., Constantinou, E., Palmer, D.B., Beier, F., Timmons, J.A., and Pitsillides, A.A. (2012). Time-series transcriptional profiling yields new perspectives on susceptibility to murine osteoarthritis. Arthritis & Rheumatism 64, 3256-3266. [view HTML]
  • Usmani, S.E., Pest, M., Kim, G.W., Ohora, S., Qin, L., and Beier, F. (2012). Transforming growth factor alpha controls the transition from hypertrophic cartilage to bone during endochondral bone growth. Bone 51, 131-141. [view HTML]
  • Fosang, A.J., and Beier, F. (2011). Emerging Frontiers in Cartilage and Chondrocyte Biology. Best Practice and Research Clinical Rheumatology 25, 751-766. [view HTML]
  • Yan, Q., Feng, Q., and Beier, F. (2012). Reduced chondrocyte proliferation, increased apoptosis and premature differentiation in neuronal nitric oxide synthase-deficient mice. Osteoarthritis & Cartilage 20, 144-151. [view HTML]
  • McErlain, D.D., Ulici, V., Darling, M., Gati, J.S., Pitelka, V., Beier, F., and Holdsworth, D.W. (2012). Initiation and progression of subchondral cysts in an in vivo, preclinical model of osteoarthritis.Arthr. Res. Therapy 14: R26. [view html]
  • Usmani, S.E*, Appleton, C.T.G., and Beier, F. (2012). Transforming growth factor alpha induces endothelin receptor A expression in osteoarthritis. J. Orthop. Res., 30 1391-1397 (Epub March 7, 2012).
  • Monemdjou R, Vasheghani F, Fahmi H, Perez G, Blati M, Taniguchi N, Lotz M, St-Arnaud R, Pelletier JP, Martel-Pelletier J, Beier F, Kapoor M. (2011) Cartilage-specific deletion of PPARγ results in abnormal endochondral ossification, and cartilage growth and development. Arthritis Rheum. 2011 Nov 30. 1551-1561. [Epub ahead of print]
  • Wang G, Yan Q, Woods A, Aubrey LA, Feng Q, Beier F. (2011) Inducible nitric oxide synthase-nitric oxide signaling mediates the mitogenic activity of Rac1 during endochondral bone growth. J Cell Sci. 2011 Oct 15;124(Pt 20):3405-13. Epub 2011 Sep 29.
  • Pitsillides AA, Beier F. (2011) Cartilage biology in osteoarthritis--lessons from developmental biology. Nat Rev Rheumatol. 2011 Sep 27;7(11):654-63. doi: 10.1038/nrrheum.2011.129.
  • Gillespie, J.R., Ulici, V., Dupuis, H., Higgs, A., DiMattia, A., Patel, S., Woodgett, J.R., and Beier, F. (2011). Deletion of Glycogen Synthase Kinase-3β in Cartilage Results in Up-Regulation of Glycogen Synthase Kinase-3a Protein Expression. Endocrinology 152, 1755-1766.
  • LeBlanc, E.A., and Beier, F. (2011). New insights in the pathobiology of cartilage degeneration: Implications for therapeutic interventions in osteoarthritis. US Musculoskeletal Review 6, 16-19.
  • Zhang, X., Siclari, V.A., Lan, S., Zhu, J., Koyama, E., Dupuis, H.L., Enomoto-Iwamoto, M., Beier, F., and Qin, L. The critical role of the epidermal growth factor receptor (EGFR) in endochondral ossification. J. Bone Miner. Res., Epub Sept. 1, 2011.
  • Stanton, L-A., Li, J.R., and Beier, F. (2010). PPAR gamma2 expression in growth plate chondrocytes is regulated by p38 and GSK-3. J. Cell. Mol. Medicine 14, 242-256.[PubMed]
  • Appleton, C.T.G., Usmani, S.E., Mort, J., and Beier, F. (2010). RhoA/ROCK and MEK/ERK mediation of transforming growth factor alpha signaling in articular cartilage degeneration. Lab. Invest. 90, 20 -30.[View HTML]
  • James, C.G., Stanton, L.-A., Agoston, H., Ulici, V., Underhill, T.M., and Beier, F. (2010). Genome-wide analyses of gene expression during mouse endochondral ossification. PLoS ONE 5, e8693.
  • Ulici, V., James, C.G., Hoenselaar, K., and Beier, F. (2010). Genome-wide analyses of PI3 kinase target genes in chondrocytes. PLoS ONE 5, e8866.
  • Yan, Q., Feng, Q., and Beier, F. (2010). Endothelial nitric oxide synthase deficiency results in reduced chondrocyte proliferation and endochondral bone growth. Arthr. & Rheum. 62, 2013-2022.
  • Ulici, V., Hoenselaar, K.D., Agoston, H., McErlain, D.D., Umoh, J., Chakrabarti, S., Holdsworth, D.W., and Beier, F. (2009). The role of Akt1 in terminal stages of endochondral bone formation: angiogenesis and ossification. Bone 45, 1133-1145.
  • Woods, A., Pala, D., Kennedy, L., McLean, S., Wang, G., Leask, A., and Beier, F. (2009). Rac1 Signaling Regulates CCN2/CTGF Gene Expression via TGFß/Smad Signaling in Chondrocytes. Osteoarthritis & Cartilage 17, 406-413. [PubMed]
  • Attur, M.G., Palmer, G.D., Al-Mussawir, H.E., Dave, M., Teixeira, C.C., Rifkin, D.B., Appleton, C.T.., Beier, F., and Abramson, S. B. (2009). F-spondin, a neuroregulatory protein, is upregulated in osteoarthritis and regulates cartilage metabolism via TGF-beta activation. FASEB J. 23, 79-89.[View HTML]
  • Wang, J., Beier, F., Tsui, H.W., and Tsui, F.W.L. (2009). The C PPDD-associated ANKH M48T mutation interrupts the interaction of ANKH with the sodium/phosphate cotransporter PiT-1. J. Rheumatology 36, 1265-1272. [View HTML]
  • Welch, I., Cowan, M., Beier, F., and Underhill, T.M. (2009). The retinoic acid binding protein Crabp2 is increased in murine models of degenerative joint disease. Arthritis Res. Ther. 11: R14. [PubMed

  • Woods, A., Wang, G., James, C.G., Dupuis, H., and Beier, F. (2009). Microarray analyses of chondrocyte gene expression in response to manipulation of the actin cytoskeleton: Identification of a central role of RORa signaling. J. Cell. Mol. Med., Epub Jan 28, 2009. [PubMed]

  • Cecil, D.L., Appleton, C.T.G., Polewski, M.D., Mort, J.S., Bendele, A., Beier, F., and Terkeltaub, R. (2009). The pattern recognition receptor CD36 is a chondrocyte hypertrophy marker associated with suppression of catabolic responses and promotion of repair responses to inflammatory stimuli. J. Immunology 182, 5024-5031.[View HTML]

  • Ulici, V., Hoenselaar, K.D., Agoston, H., McErlain, D.D., Umoh, J., Chakrabarti, S., Holdsworth, D.W., and Beier, F. (2009). The role of Akt1 in terminal stages of endochondral bone formation: angiogenesis and ossification. Bone , Epub Aug. 10, 2009. [PubMed]
  • Appleton, C.T.G., Usmani, S.E., Mort, J., and Beier, F. (2009). Rho/ROCK and MEK/ERK activation by transforming growth factor-alpha induces articular cartilage degradation. Lab. Invest., Epub Oct. 12, 2009. [View HTML]
  • Solomon, L., Li, J., Bérubé, N.G., and Beier, F. (2009). Loss of ATRX function in cartilage results in only minor skeletal defects. PLoS ONE 4, e7106.[View HTML]
  • Ulici, V., Hoenselaar, K.D., Gillespie, J.R., and Beier, F. (2008). The PI3K pathway regulates endochondral bone growth through control of hypertrophic chondrocyte differentiation. BMC Dev. Biol. 8:40. [View HTML]
  • Solomon, L.A., Bérubé, N.G., and Beier, F. (2008). Transcriptional regulators of chondrocyte hypertrophy. Birth Defects Research – Embryo Today 82, 123-130. [PubMed]
  • Stanton, L.A., Li, J., and Beier, F. (2008). PPARγ2 expression in growth plate chondrocytes is regulated by p38 and GSK-3. J Cell Mol Medicine, Epub June 20, 2008.[PubMed]
  • Teixeira, C., Agoston, H., and Beier, F. (2008). Nitric oxide, C-type natriuretic peptide and cGMP as regulators of endochondral ossification. Dev Biol, 319, 171-178. [PubMed]
  • Gill, K.S., Beier, F., and Goldberg, H. (2008). Rho-Rock Signaling Differentially Regulates Chondrocyte Spreading on Fibronectin and Bone Sialoprotein. Am J Physiology: Cell Physiology 295, C38-49.[PubMed]
  • Pala, D., Woods, A., Kennedy, L., Liu, S., Chen, S.,Bursell, L., Lyons, K.M., Carter, D.E., Beier, F., and Leask, A. (2008) Focal adhesion kinase/Src suppresses early chondrogenesis: central role of CCN2. J Biol Chem 283(14):9239-9247. [PubMed]
  • McErlain DD, Appleton CT, Litchfield RB, Pitelka V, Henry JL, Bernier SM, Beier F, Holdsworth DW. (2008) Study of subchondral bone adaptations in a rodent surgical model of OA using in vivo micro-computed tomography. Osteoarthritis Cartilage 16(4): 458-469.[PubMed]
  • Bursell, L., Woods, A., James, C.G., Pala, D., Leask, A., and Beier, F. (2007) Src kinase inhibition promotes the chondrocyte phenotype. Arthritis Res Ther 9(5):R105. [PubMed]
  • Woods, A., Khan, S., and Beier, F. (2007) C-Type natriuretic peptide regulates cellular condensation and glycosaminoglycan synthesis during chondrogenesis. Endocrinology [PubMed]
  • Appleton, C.T., Usmani, S.E., Bernier, S.M., Aigner, T. and Beier, F. (2007) Transforming growth factor alpha suppresses chondrocyte phenotype and Sox9 expression in experimental osteoarthritis. Arthritis Rheum 56(11):3693-3705.[View HTML]
  • James, C.G., Ulici, V., Tuckermann, J., Underhill, T.M. and Beier, F. (2007) Expression profiling of Dexamethasone-treated primary chondrocytes identifies targets of glucocorticoid signalling in endochondral bone development. BMC Genomics 8:205. [View HTML]
  • Woods, A., Wang, G., Dupuis, H., Shao, Z., and Beier, F. (2007) Rac1 Signaling Stimulates N-Cadherin expression, mesenchymal condensation and chondrogenesis. J Biol Chem 282(32):23500-8. [View HTML]
  • Wang, G., Woods, A., Agoston, H., Ulici, V., Glogauer, M., and Beier, F. (2007) Genetic Ablation of Rac1 in Cartilage Results in Chondrodysplasia. Dev Biol 306:612-623. [View HTML]
  • Agoston, H., Khan, S., James, C.G., Gillespie, J.R., Serra, R., Stanton, L.-A., and Beier, F. (2007) C-type natriuretic peptide regulates endochondral bone growth through p38 MAP kinase-dependent and -independent pathways. BMC Developmental Biology 7:18. [View HTML]
  • Woods, A., Wang, G. and Beier, F. (2007) Regulation of Chondrocyte Differentiation by the Actin Cytoskeleton and Adhesive Interactions. J Cell Physiol. 2007 Oct;213(1):1-8.[PubMed]
  • Appleton, C.T.G., Pitelka, V., Henry, J.L., and Beier, F. (2007) Genome-wide analyses of gene expression in early experimental osteoarthritis. Arthritis Rheum 56(6):1854-1868.[PubMed]
  • Appleton, C.T.G., McErlain, D.D, Pitelka, V., Schwartz, N., Bernier, S.M., Henry, J.L., Holdsworth, D.W., and Beier, F. (2007) Forced mobilization accelerates pathogenesis: Characterization of a pre-clinical surgical model of osteoarthritis. Arthitis Res Ther 9(1):R13. [PubMed]


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