In:
Arthritis & Rheumatology, Wiley, Vol. 66, No. 4 ( 2014-04), p. 831-840
Abstract:
During development of the vertebrate skeleton, chondrocytes form a cartilage template that is gradually replaced by bone. Hormones of the Hedgehog (HH) family have been implicated in the ossification process, but their exact relationship to normal or pathogenic bone formation is unclear. This study was undertaken to establish a genetic tool that allows the discrete inactivation of genes in spinal chondrocytes, and to investigate in vivo how chondrocyte‐specific ablation of the inhibitory HH receptor Patched 1 ( Ptch1) affects skeleton integrity. Methods A Cre ‐deleter mouse strain, mb1‐Cre , for selective gene recombination in spinal chondrocytes was identified by in situ hybridization and histologic analysis. The mb1‐Cre +/− animals were crossed with mice that harbor a loxP‐flanked Ptch1 gene ( Ptch1 flox/flox ) to abrogate the inhibition of the HH signaling pathway in chondrocytes. The skeletal integrity of F1 mice was characterized by high‐resolution flat‐panel–based volume computed tomography and histologic staining procedures. Results During the first weeks after birth, all mb1‐Cre +/− / Ptch1 flox/flox mice developed progressive spinal fusion with malformation of the vertebrae. This phenotype was caused by aberrant chondrocyte proliferation in the intervertebral discs that blocked endochondral ossification. Importantly, the disease pattern occurred in an inflammation‐independent manner. Conclusion Our findings indicate that chronic activation of the HH signal pathway in spinal chondrocytes can trigger an ankylosing spine morphology without immune cell contributions. Hence, the destruction of cartilage and loss of axial joint integrity can result from chondrocyte‐intrinsic defects of monogenic origin.
Type of Medium:
Online Resource
ISSN:
2326-5191
,
2326-5205
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2754614-7
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