Understanding the cell and molecular biology of growth plate chondrocyte differentiation, maturation and apoptosis has been the focus of my research interest. I have shown that maturation is coupled to a loss of the cell reductive reserve and characterized the anti-oxidant system of hypertrophic chondrocytes with respect to enzymes that protect cells from oxidative stress. I have also clarified the relationship between the maturation-dependent loss of thiols and the expression of the hypertrophic phenotype. Within the past 3 years, I have provided strong evidence to support the hypothesis that the terminally differentiated chondrocyte is removed from the epiphysis by apoptosis. Results from these studies show that inorganic phosphate, an anion present in high concentrations in the calcified cartilage zone of the growth plate, is an efficient apoptogen - http://www.nyu.edu/dental/faculty/directory/chondrocyte.html. Furthermore, I have characterized the transport systems mediating Pi loading of these cells. A major focus of my recent studies has been to define the role of nitric oxide (NO) in Pi-induced apoptosis. As I became involved in the study of the NO complex signaling mechanisms, I have found that this gas has a global role in regulating chondrocyte terminal differentiation.

My current research interests can be divided into four major areas. First, I am completing the studies of the mechanism of Pi induced apoptosis in chondrocyte and will dissect the role of mitochondria in this process. Thurs, my work focus on these organelles and NO, which has been described as a potent inhibitor of mitochondrial function. A second area of interest is to elucidate the function of NO in chondrogenesis. A detailed study of the endothelial nitric oxide synthase (eNOS) knockout mouse, which presents marked limb defects, will be carried out. In addition, eNOS deficient mesenchymal cells will be used to explore the importance of eNOS in chondrogenesis. Taking advantage of embryonic manipulation techniques (in ovo), I plan to gain information on how overexpression of NO syntheses affects endochondral bone formation. My third area of interest involves the investigation of hypoxia as an inducer of chondrogenic differentiation. My preliminary work and studies from other laboratories suggest that hypoxia is associated with the establishment of a chondrogenic lineage. Special attention will be given to mapping of hypoxic regions during embryonic development and the differential expression of hypoxia-induced genes. Finally, and in collaboration with the Biomaterials Department at NYU, knowledge acquired from studies of physiology of growth plate cartilate are being used as a platform for a totally new approach to tissue engineering of bone. Studies currently underway in my laboratory will attempt to generate endochondral bone in vitro.

Teixeira, M. Hatori, P. S. Leboy, M. Pacifici, I. M. Shapiro, A Rapid and Ultrasensitive Method For Measurement of DNA, Calcium and Protein Content, and Alkaline Phosphatase Activity of Chondrocyte Cultures, Calcif Tissue Int (1995) 56: 252-256.

M. Hatori, J. Sparkman, C. C. Teixeira, M. Grynpas, J. Nervina, N. Olivieri, I. M: Shapiro, Effects of Deferoximine on Chondrocyte Alkaline Phosphatase Activity: Proxidant Role of Deferoximine in Thalassemia, Calcif Tissue Int (1995) 57: 229-236.

Masashi Hatori, Kevin Klatte, Cristina C. Teixeira, and Irving M. Shapiro, End Labeling Studies of fragmented DNA in the Avian Growth Plate: Evidence of Apoptosis in Terminally Differentiated Chondrocytes, J Bone and Mineral Research (1995) Vol10, 12:1960-1968.

Masashi Hatori, Cristina C. Teixeira, Kristine Debolt, Maurizio Pacifici, and Irving Shapiro, Adenine Nucleotide Metabolism by Chondrocytes In Vitro: Role of ATP In Chondrocyte Maturation and Matrix Mineralization, J Cellular Physiology (1995) 165:468-479.

Ramesh Rajpurohit, Cameron J. Koch, Zhuliang Tao, Cristina C Teixeira, and Irving Shapiro, Adaptation of Chondrocytes to Low Oxygen Tension: Relationship Between Hypoxia and Cellular Metabolism, J of Cellular Physiology (1996) 168:424-432.

C. C. Teixeira, I.M. Shapiro, M. Hatori, R. Rajpurohit and C. J. Koch, Retinoic Acid Modulation of Glutathione and Cysteine Metabolism in Chondrocytes, Biochem J (1996) 314:21-26.

Shapiro, K. Mansfield, Z. Tao, K. Ohyama, C Teixeira, C Chung, C Koch, R Rajpurohit, Oxygen Regulation of Chondrocyte Function: Reevaluation of the Hypothesis that Cells in the Growth Plate are Hypoxic. In Skeletal Growth and Development: Clinical Issues and Basic Science Advancements, (1998) by the American Academy of Orthopedic Surgeons (First Edition)

Cristina C. Teixeira, Irving M. Shapiro, Masashi Hatori, Ramesh Rajpurohit and Cameron Koch, Retinoic Acid Modulation of Glutathione and Cysteine Metabolism in Chondrocytes, Biochem J (1996) 314:21-26. early tooth development, Clinical Orthodontics and Research, (1999) 2:171-174

Cristina C. Teixeira, New horizons in understanding early tooth development, Clinical Orthodontics and Research, (1999) 2:171-174

Kyle Mansfield, Cristina C. Teixeira, Christopher Adams and Irving Shapiro, Phosphate Ions Mediate Chondrocyte Apoptosis Through a Plasma Membrane Transporter Mechanism, Bone (2001) 28 (1): 1-8

Cristina C. Teixeira, Kyle Mansfield, Caryn Hertkorn, Harry Ischiropoulos, Irving M. Shapiro, Pi-induced Chondrocyte Apoptosis is Linked to Nitric Oxide Generation, American J of Physiology (2001) 281: C833-C839

C. S. Adams, K. D. Mansfield, R. Rajpurohit, H. Tachibana, C.C. Teixeira and I. M. Shapiro, Components of the Cartilage Extracellular Matrix Regulate Chondrocyte Apoptosis. In: Shapiro IM, Handerson, HC, Boyan B(ed) The Growth Plate (2002), IOS Press, Amsterdam

Cristina C. Teixeira, Harry Ischiropoulos, Phoebe Leboy and Irving M Shapiro, Nitric Oxide Mediates Retinoic Acid-Induced Chondrocyte Maturation (submitted for publication)

Cristina C. Teixeira, Ramesh Rajpurohit, Kyle Mansfield, Cameron J. Koch and Irving Shapiro, Maturation Dependent Thiol Loss Increases Susceptibility to Apoptosis, J Bone and Min Res (2003) 18 (4):662-668