Roland M. Leach, Ph.D.
- NUTRN 582 (Lectures in) Regulation of Nutrient Metabolism
- PHYSIO 572 (Lectures in) Animal Physiology
The overall goal of our research program is to define the role of nutrients, systemic hormones, and locally produced growth factors in longitudinal bone growth. Defects in this process account for many of the major types of skeletal deformities that occur in broilers and turkeys.
We are investigating two "loops" that are critical in endochondral bone formation. One is the bFGF-FGF receptor loop. Research with transgenic animals and genetic mutants has demonstrated that this loop is critical for longitudinal bone growth.
The second "loop" that we are investigating is the PTH/PTHr - receptor loop. PTHrP is a PTH-like peptide that is found in a number of tissues. It has been demonstrated that PTHrP is essential for normal skeletal development.
FGF-FGF Receptor Loop
: There are nineteen
different FGFs (FGF-1 through FGF-19). Four of these--2, 4, 8, and
10--are critical for embryonic limb development. However, we have only
been able to identify FGF-1 and FGF-2 in postnatal chick cartilage. When
the biological activity of the various FGFs were tested, we found
FGF-1, 2, 4, 8, and 9 to have mitogenic activity with proliferative
growth plate chondrocytes. This information in combination with the fact
that receptors CEK-1 and CEK-2 are present in these cells provides some
insight into the receptor aspects of signal transduction. We are
currently attempting to further determine which forms of FGF are
actually present in cartilage tissue. Western blotting techniques are
being applied to cell lysates of chondrocytes obtained from different
morphological cartilage zones. PCR is being used to identify which genes
are actually expressed in growth plate cartilages.
PTHrP in the Epiphyseal Growth Plate : We have found immunoactivity of PTHrP to be highest in the perichondrium adjacent to articular and growth plate cartilage tissue. In the growth plate, immunostaining was most intense in hypertrophic chondrocytes. This observation does not support the widely held hypothesis that the perichondrium is the key source of PTHrP for growth plate signalling. Western blotting of lysates of growth plate chondrocytes has shown that the PTHrP has an estimated mw of 14,400 kDa.
We will continue to study the sequence of events that are associated with the differentiation of growth plate chondrocytes.
A new thrust of our research deals with medullary bone development and metabolism. In the laying hen, this bone cycles on a daily basis and makes a significant contribution to eggshell calcuim. Of particular interest is identifying and characterizing the matrix proteins that are unique to medullary bone.
Knopov, V., R. M. Leach, T. Barak-Shalom, S. Hurwitz, and M. Pines. 1995. "Osteopontin gene expression and alkaline phosphatase activity in avian tibial dyschondroplasia." Bone 16:329S-334S.
Twal, W. O., Wu, C. V. Gay, and R. M. Leach, Jr. 1996. "Immunolcocalization of basic fibroblastic growth factor in avian tibial dyschondroplastic cartilage." Poultry Sci. 75:130-34.
Luan, Y. J., C. A. Praul, C. V. Gay, and R. M. Leach, Jr. 1996. "Basic fibroblast growth factor: An autocrine growth factor for epiphyseal growth plate chondrocytes." J. Cell. Biochem. 62:372-82.
Twal, W. O. and R. M. Leach. 1996. "Isolation and characterization of microvascular endothelial cells from chicken fat pads." In Vitro Cell. Dev-An . 32:403-8.
Wu, J., M. Pines, C. V. Gay, S. Hurwitz, and R. M. Leach, Jr. 1996. "Immunolocalization of osteonectin in avian tibial dyschondroplastic cartilage." Dev. Dynam. 207:69-74.
Pines, M., V. Knopov, O. Genia, S. Hurwitz, A. Faerman, L. C. Gerstenfeld, and R. M. Leach. 1998. "Development of avian tibial dyschondroplasia:Gene expression and protein synthesis." Calcif. Tissue Int. 63:521-27.
Ben-Bassat, S., O. Genina, I. Lavelin, R. M. Leach, and M. Pines. 1999."Parathyroid receptor gene expression by epiphyseal growth plates in rickets and tibial dyschondroplasia." Mol. Cell. Endocrinol. 149:185-95.
Pines, M., N. Yarden, S. Ben-Bassat, I. Lavelin, and R. M. Leach. 1999. "Regulation of the calcium-sensing and parathyroid hormone receptor genes in the chick." In: Calcium Metabolism: Comparative Endocrinology. Colchester, U.K.: Portland Press, 1999; pp. 67-73.
Praul, C. A., B. C. Ford, C. V. Gay, M. Pines, and R. M. Leach. 2000. "Gene expression and tibial dyschondroplasia." Poultry Sci. 79:1009-13.
N. J., C. A. Praul, B. C. Ford, and R. M. Leach. 2001. "Parathyroid
hormone-related peptide expression in the epiphyseal growth plate of the
juvenile chicken: Evidence for the origin of the parathyroid
hormone-related peptide found in the epiphyseal growth plate."
J. Cell. Biochem.
Rousche, K. T., C. A. Praul, and R. M. Leach. 2001. "The use of growth factors in the proliferation of avian articular chondrocytes in a serum-free culture system." Connect. Tissue Res. 42:165-74.
Praul, C. A., B. C. Ford, and R. M. Leach. 2002. "Effect of fibroblast growth factors 1, 2, 4, 5, 6, 7, 8, 9, and 10 on avian chondrocyte proliferation." J. Cell. Biochem. 84:359-66.
Wang, X., B. C. Ford, C. A. Praul, and R. M. Leach, Jr. 2002. "Collagen X expression in oviduct tissue during the different stages of the egg laying cycle." Poultry Sci. 81:805-8.
Wang, X., G. J. Fosmire, C. V. Gay, and R. M. Leach, Jr. 2002. "Short-term zinc deficiency inhibits chondrocyte proliferation and induces cell apoptosis in the epiphyseal growth plate of young chickens." J. Nutr. 132:665-73.
Luo, X. M., G. J. Fosmire, and R. M. Leach, Jr. 2002. "Chicken keel cartilage as a source of chondroitin sulfate." Poultry Sci. 81:1086-89.
Kim, W. K., B. C. Ford, A. D. Mitchell, R. G. Elkin, and R. M. Leach. 2004. "Comparative assessment of bone among wild-type, restricted ovulator and out-of-production hens." Br. Poultry Sci. 45:463-470.
Wang, Xibin, B. C. Ford, C. A. Praul, and R. M. Leach, Jr. 2005. "Characterization of the non-collagenous proteins in avian cortical and medullary bone." Comp. Biochem. Physiol. Part B 140:665-672.