Septoclast deficiency accompanies postnatal growth plate chondrodysplasia in the toothless (tl) osteopetrotic, colony-stimulating factor-1 (CSF-1)-deficient rat and is partially responsive to CSF-1 injections
Authors
Gartland, AlisonMason-Savas, April
Yang, Meilheng
MacKay, Carole A.
Birnbaum, Mark J.
Odgren, Paul R.
UMass Chan Affiliations
Department of Orthopedics and Physical RehabilitationDepartment of Cell Biology
Document Type
Journal ArticlePublication Date
2009-11-07Keywords
AnimalsBone Development
Bone Diseases, Developmental
Cartilage
Chondrocytes
Growth Plate
Immunohistochemistry
Macrophage Colony-Stimulating Factor
Neovascularization, Physiologic
Osteopetrosis
Rats
Rats, Mutant Strains
Cell Biology
Metadata
Show full item recordAbstract
The septoclast is a specialized, cathepsin B-rich, perivascular cell type that accompanies invading capillaries on the metaphyseal side of the growth plate during endochondral bone growth. The putative role of septoclasts is to break down the terminal transverse septum of growth plate cartilage and permit capillaries to bud into the lower hypertrophic zone. This process fails in osteoclast-deficient, osteopetrotic animal models, resulting in a progressive growth plate dysplasia. The toothless rat is severely osteopetrotic because of a frameshift mutation in the colony-stimulating factor-1 (CSF-1) gene (Csf1(tl)). Whereas CSF-1 injections quickly restore endosteal osteoclast populations, they do not improve the chondrodysplasia. We therefore investigated septoclast populations in Csf1(tl)/Csf1(tl) rats and wild-type littermates, with and without CSF-1 treatment, at 2 weeks, before the dysplasia is pronounced, and at 4 weeks, by which time it is severe. Tibial sections were immunolabeled for cathepsin B and septoclasts were counted. Csf1(tl)/Csf1(tl) mutants had significant reductions in septoclasts at both times, although they were more pronounced at 4 weeks. CSF-1 injections increased counts in wild-type and mutant animals at both times, restoring mutants to normal levels at 2 weeks. In all of the mutants, septoclasts seemed misoriented and had abnormal ultrastructure. We conclude that CSF-1 promotes angiogenesis at the chondroosseous junction, but that, in Csf1(tl)/Csf1(tl) rats, septoclasts are unable to direct their degradative activity appropriately, implying a capillary guidance role for locally supplied CSF-1.Source
Am J Pathol. 2009 Dec;175(6):2668-75. Epub 2009 Nov 5. Link to article on publisher's siteDOI
10.2353/ajpath.2009.090185Permanent Link to this Item
http://hdl.handle.net/20.500.14038/42874PubMed ID
19893052Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.2353/ajpath.2009.090185