Collagen IX is indispensable for timely maturation of cartilage during fracture repair in mice.
Fracture repair recapitulates in adult organisms the sequence of cell biological events of endochondral ossification during skeletal development and growth. After initial inflammation and deposition of granulation tissue, a cartilaginous callus is formed which, subsequently, is remodeled into bone. In part, bone formation is influenced also by the properties of the extracellular matrix of the cartilaginous callus. Deletion of individual macromolecular components can alter extracellular matrix suprastructures, and hence stability and organization of mesenchymal tissues. Here, we took advantage of the collagen IX knockout mouse model to better understand the role of this collagen for organization, differentiation and maturation of a cartilaginous template during formation of new bone. Although a seemingly crucial component of cartilage fibrils is missing, collagen IX-deficient mice develop normally, but are predisposed to premature joint cartilage degeneration. However, we show here that lack of collagen IX alters the time course of callus differentiation during bone fracture healing. The maturation of cartilage matrix was delayed in collagen IX-deficient mice calli as judged by collagen X expression during the repair phase and the total amount of cartilage matrix was reduced. Entering the remodeling phase of fracture healing, Col9a1(-/-) calli retained a larger percentage of cartilage matrix than in wild type indicating also a delayed formation of new bone. We concluded that endochondral bone formation can occur in collagen IX knockout mice but is impaired under conditions of stress, such as the repair of an unfixed fractured long bone.
Opolka
Alfred
A
Department of Orthopaedic Surgery, Experimental Orthopaedics, University Hospital of Regensburg, Germany.
Ratzinger
Sabine
S
Schubert
Thomas
T
Spiegel
Hans-Ulrich
HU
Grifka
Joachim
J
Bruckner
Peter
P
Probst
Axel
A
Grässel
Susanne
S
D000818:Animals; D002356:Cartilage / Q000254:growth & development* / Q000378:metabolism; D024081:Collagen Type IX / Q000235:genetics / Q000378:metabolism*; D017102:Fracture Healing / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology*; D013977:Tibia / Q000293:injuries* / Q000502:physiology
D024081:Collagen Type IX