Bone and soft connective tissue alterations result from loss of fibrillin-2 expression.
Fibrillins 1, 2 and 3 make up a family of genes that encode large, cysteine-rich extracellular matrix glycoproteins found in connective tissues, lung, blood vessels and other extensible tissues. Fibrillins 1 and 2 have both overlapping as well as separate distributions in human embryonic and adult tissues. Fibrillin-containing microfibrils are known to modulate morphogenetic events by proper targeting of growth factors to the extracellular matrix. Mutation of the fibrillin-2 gene causes a genetic disorder, congenital contractural arachnodactyly (CCA), that results in flexion contractures. Previously, we have shown a distinct fibrillin-2 distribution in the pericellular matrix of interior tenocytes and later demonstrated a unique fibrillin-2 containing structure that runs along the tendon cell arrays in the canine flexor tendon. We hypothesized that loss of these fibrillin-2 containing structures might affect normal tendon development. To test our hypothesis, connective tissues from mice null for fibrillin-2 gene expression were studied. Murine flexor digitorum longus tendons were evaluated for total collagen content, and the intermolecular collagen cross-links hydroxylysyl and lysyl pyridinoline. The results show decreased collagen cross-links in fibrillin-2 null mice, however total collagen content remained the same when compared to wild type. Bone morphology was studied using micro computed tomography (CT). Fibrillin-2 null mice display a focal area of decreased bone length in the extremities as compared to wild type mice. Together, these results demonstrate a role for fibrillin-2 in bone and soft connective tissue morphological and biochemical processes.
Division of Musculoskeletal Sciences, Department of Orthopedics, H089, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033-0850, United States.
Rajeev
R
Boregowda
Emmanuel
E
Paul
Jason
J
White
Timothy M
TM
Ritty
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D003238:Connective Tissue / Q000378:metabolism*; D005260:Female; D000071840:Fibrillin-2; D000071837:Fibrillins; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission
C000605723:FBN2 protein, human; C000605728:Fbn2 protein, mouse; D000071840:Fibrillin-2; D000071837:Fibrillins; D008840:Microfilament Proteins; D003094:Collagen