Scope of work: Studies in this laboratory are directed at an understanding of the
mechanisms which are operant in the pathophysiology of destructive diseases of the middle ear,
including cholesteatoma, chronic otitis media and otosclerosis.
One of the characteristics of these diseases is that they result in localized
bone resorption and remodeling. Most of the studies in this laboratory are
directed at an understanding of the cellular and molecular control of the resorbing cells, the osteoclasts.
Osteoclasts are activated under a variety of experimental conditions, including an experimental cholesteatoma
developed in this laboratory in the Mongolian gerbil and models of localized bone resorption in vivo and in vitro
in murine cell and organ cultures.
A number of factors have been identified which are active in these systems, including arachidonic acid
metabolites, the cytochrome P-450 III-a system, nitric oxide synthase, catecholamines, neuropeptides such as
substance P, and the interleukin-1 family of cytokines. The control of osteoclast activity at a local site is regulated
by the interaction of several of the above mentioned factors.
The techniques used in our laboratory are:
1) Induction of cholesteatomas in gerbils and mice.
2) In vivo bone resorption.
3) Keratin particle induced osteolysion osteoclastic bone resorption in the mouse calvarian.
4) In vitro resorption of Ca45 prelabeled mouse calvaria.
5) Isolated osteoclast cultures from murine sources - wild type and genetic knockout varieties.
6) Immunohistochemistry
7) RT-PCR, in situ hybridization, immunoblotting, histomorphometry and electron microscopy.
PUBLICATIONS
1. Chole, R.A., Tinling, S.P., Leverentz, E., McGinn, M.D. Inhibition of nitric oxide synthase blocks osteoclastic bone resorption in adaptive bone modeling. Acta Oto-Laryngologica, 118:705-711, 1998
2. Chole, R.A. The molecular biology of bone resorption due to chronic otitis media. An NY Acad Sci. 830:95-109, December 29, 1997.
3. Chole, R.A. and Kim, H.J. Ossiculoplasty with presculpted banked cartilage. Operative Techniques in Otolaryngology-Head and Neck Surgery, 7(1):38-44, March, 1996.
4. Chole, R.A. Differential osteoclast activation in endochondral and intramembranous bone. Annals of Otology, Rhinology, and Laryngology 102(8) 616-619, August 1993.
5. Chole, R.A., Tinling, S.P., Faddis, B.T. Human recombinant Interleukin-1 receptor antagonist blocks bone resorption induced by interleukin-b, but not interleukin-a. Calcified Tissue International, 55:12-15, 1994.