Jorge N. Artaza, Ph.D.

Jorge N. Artaza, Ph.D.

Jorge N. Artaza, Ph.D.
Research Assistant Professor
Charles Drew University of Medicine and Science
Hawkins Bldg, Room 3084
1731 E. 120th Street
Los Angeles, CA 90059

Phone: (323) 563-4915
Fax: (323) 563-9352
 joartaza@cdrewu.edu

Research Interests

Stem cells are pluripotent cells able to proliferate and differentiate into a variety of cell lineages, and although they have been extensively studied in embryonic tissues and in the adult bone marrow, they have been recently detected in most tissues in young and adult animals, and specifically in skeletal muscle. Adult muscle stem cell (AMSC) differentiation is assumed to be involved in two processes controlling skeletal muscle mass and composition: 1) muscle degeneration through fat and connective tissue infiltration in dystrophies, and to a lesser degree in aging; and 2) muscle regeneration subsequent to muscle fiber loss after injury, heavy exercise, wasting, and similar conditions. Endogenous AMSC differentiation can be studied in animal models, and exogenous pluripotent cells from various origins can also be implanted in the skeletal muscle of recipient animal models to study the effect of endogenous factors that modulate their differentiation and the efficacy of transplant myogenesis. One of these factors is assumed to be the negative regulator of skeletal muscle mass, myostatin (Mst), which we propose inhibits myogenic differentiation and promotes adipogenesis in AMSC.

Of the several animal models used to study myogenesis and adipogenesis in skeletal muscle, my research interests include the mdx mouse (a model of Duchenne's muscular dystrophy) which has the advantage of displaying the two main features of muscle degeneration: the loss of muscle fibers and their replacement by fat cells and fibroblasts that suggest an altered differentiation of AMSC. The molecular defect, the inactivation of the dystrophin gene, can be partially compensated for by implanting normal AMSC. Myostatin is expressed in the regenerating muscle of this mouse, and Mst inhibition by Mst antibodies, or crossing of mdx mouse with the Mst Knock out (-/-) mouse, attenuates the severity of the dystrophy. Mst (-/-) and Mst over-expressing transgenic mice, which are available, can be used both as a source of AMSC and as hosts for transplant of AMSC.

Our group has studied the role of Mst in skeletal muscle growth and differentiation, has generated a Mst over-expressing transgenic mouse, and has reported the modulation of myogenic and adipogenic differentiation of mesenchymal pluripotent cells in vitro.

The goal of my research is to investigate whether:

  1. Mst inhibits in vitro differentiation of mesenchymal pluripotent cells into the myogenic lineage and promotes the commitment of these cells into the adipogenic lineage,
  2. These Mst effects are exerted through the modulation of the Smad or Wnt signaling cascades; and
  3. Blocking Mst expression or activity can promote myogenic transformation of endogenous and transplanted pluripotent stem cells in the mdx mouse
The results from these studies may help to clarify the role of myostatin in inducing muscle degeneration by driving AMSC away from myogenesis, or interfering with muscle regeneration, during anabolic interventions aimed to correct the loss of skeletal muscle mass in aging-related sarcopenia and other wasting conditions.

SOME RELEVANT PUBLICATIONS

Artaza JN, R. Singh, MG. Ferrini, M. Braga J. Tsao and N. Gonzalez-Cadavid. Myostatin Promotes a fibrotic phenotypic switch in multipotent C3H 10T1/2 cells without affecting their differentiation into myofibroblasts. Journal of Endocrinology, in press, Nov; 2007.

Artaza JN, Reisz-Porszasz S, Dow JS, Kloner RA, Tsao J, Bhasin S, Gonzalez-Cadavid NF. Alterations in myostatin expression are associated with changes in cardiac left ventricular mass but not ejection fraction in the mouse. Journal of Endocrinolgy 2007 Jul; 194(1): 63-76.[abstract]

Magee, T.R., Artaza,J. N., Ferrini, M. G., Zuniga, F. I., Cantini, L., Reisz-Porszasz, S., Rajfer, J., and Gonzalez-Cadavid, N. F., 2006. Myostatin short hairpin RNA gene therapy increases muscle mass. Journal of Gene Medicine  8(9):1171-1181.  [abstract]

Singh, R., Artaza, J. N., Taylor, W. E., Braga, M., Gonzalez-Cadavid, N. F., and  Bhasin, S. 2006. Testosterone Inhibits Adipogenic Differentiation in 3T3-L1 cells: Possible Role of Androgen Receptor induced Nuclear Translocation of beta-catenin and activation of Wnt Signaling.  Endocrinology 147(1):141-54.   [abstract]

Jasuja, R., Catlin, D.H., Miller, A., Chang, Y.C., Herbst, K.L., Starcevic, B., Artaza, J.N., Singh, R., Datta, G., Sarkissian, A., Subarathnam, C., Baker M., and Bhasin, S. 2005. S.Tetrahydrogestrinone is an Androgenic Steroid that Stimulates Androgen-Receptor Mediated Myogenic Diferentiation in C3H10T (1/2) Multipotent Mesenchymal cells and Promotes Muscle Accretion in Orchidectomized Male Rats. Endocrinology 146(10):4472-8. [abstract]

Artaza,J.N., Bhasin, S., Magee T.R., Reisz-Porszasz, S., Shen R., Groome,N.P., Fareez, M.M., and Gonzalez-Cadavid, N.F. 2005. Myostatin Inhibits Myogenesis and Promotes Adipogenesis in 10T (1/2) Mesenchymal Multi-potent cells. Endocrinology 146(8):3547-57. [abstract]

Singh, R., Artaza, J.N., Taylor, W.E., Gonzalez-Cadavid, N.F., and Bhasin, S. 2003. Androgens Stimulate Myogenic Differentiation and Inhibit Adipogenesis in C3H 10T1/2 pluripotent cells Through an Androgen Receptor-Mediated Pathway. Endocrinology 144(11):5081-8.  [abstract]

Bhasin, S., Taylor, W.E., Singh, R., Artaza, J., Sinha-Hikim I., Choi, H., Jasuja, R., and Gonzalez-Cadavid, N.F. 2003. The Mechanisms of Androgen Effects on Body Composition: Mesenchymal Pluripotent Cell as the Target of Androgen Action. J Gerontol A Biol Sci Med Sci. 58(12): M1103-10. [abstract]

Reisz-Porszasz, S., Bhasin, S., Artaza, J.N., Shen, R., Sinha-Hikim, I., Hogue, A., Fielder, T.J., and Gonzalez-Cadavid, N.F. 2003. Lower Skeletal Mass in Male Transgenic Mice with Muscle-Specific Hyperexpression of Myostatin. Am J Physiol Endocrinol Metab  285(4): E876-88. [abstract]

Artaza, J.N., Bhasin, S., Mallidis, C., Taylor, W. E., Ma, K., and Gonzalez-Cadavid, N. 2002. Endogenous Expression and localization of Myostatin and its relation to MHC distribution in C2C12 skeletal muscle cells. Journal of Cellular Physiology 190(2): 170-179.  [abstract]

Last updated 11/27/07