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Journal of Histochemistry and Cytochemistry, Vol. 45, 1069-1082, Copyright © 1997 by The Histochemical Society, Inc.

ARTICLE

Fibrillin-1 in Human Cartilage: Developmental Expression and Formation of Special Banded Fibers

Douglas R. Keenea, C. Diana Jordanc, Dieter P. Reinhardta, Catherine C. Ridgwaya, Robert N. Onoa, Glen M. Corsona, Margaret Fairhursta, Michael D. Sussmana, Vincent A. Memolic, and Lynn Y. Sakaia,b
a Shriners Hospital for Children, Portland, Oregon
b Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland, Oregon
c Department of Pathology, Dartmouth Medical Center, Lebanon, New Hampshire

Correspondence to: Lynn Y. Sakai, Shriners Hospital for Children, 3101 SW Sam Jackson Park Rd., Portland, OR 97201.

The molecular basis for Marfan's syndrome (MS), a heritable disorder of connective tissue, is now known to reside in mutations in FBN1, the gene for fibrillin-1. Classic phenotypic manifestations of MS include several skeletal abnormalities associated primarily with overgrowth of long bones. As a first step towards understanding how mutations in FBN1 result in skeletal abnormalities, the developmental expression of fibrillin-1 (Fib-1) in human skeletal tissues is documented using immunohistochemistry and monoclonal antibodies demonstrated here to be specific for Fib-1. At around 10-11 weeks of fetal gestation, Fib-1 is limited in tissue distribution to the loose connective tissue surrounding skeletal muscle and tendon in developing limbs. By 16 weeks, Fib-1 is widely expressed in developing limbs and digits, especially in the perichondrium, but it is apparently absent within cartilage matrix. Fib-1 appears as a loose meshwork of fibers within cartilage matrix by 20 weeks of fetal gestation. Until early adolescence, Fib-1 forms loose bundles of microfibrils within cartilage. However, by late adolescence, broad banded fibers composed of Fib-1 are found accumulated pericellularly within cartilage. Because these fibers can be extracted from cartilage using dissociative conditions, we postulate that they are laterally packed and crosslinked microfibrils. On the basis of these findings, we suggest that the growth-regulating function of Fib-1 may reside persistently within the perichondrium. In addition, the accumulation of special laterally crosslinked Fib-1 microfibrils around chondrocytes during late adolescence suggests that growth-regulating activities may also be performed by Fib-1 at these sites. (J Histochem Cytochem 45:1069-1082, 1997)

Key Words: fibrillin, cartilage, microfibrils, Marfan's syndrome, special banded fibers


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