Chondrocytic EphrinB2 promotes cartilage destruction by osteoclasts in endochondral ossification

Abstract

There was an error published in Development 143, 648-657.In the Materials and Methods section the murine Efnb2 gene mutation was incorrectly listed as Efnb2 tm1And . The correct annotation for the floxed allele that we used in our experiments is Efnb2 tm2And . This was a nomenclature error and does not affect the results or conclusions of the paper.We thank Monika Tomczuk, scientific curator of Mouse Genome Informatics at The Jackson Laboratory, for alerting us to this mistake.We apologise for any confusion that this error may have caused. Osteoclasts at the growth plate had an abnormal morphology and expressed low levels of tartrate-resistant acid phosphatase; this was not observed in more mature bone. Electron microscopy revealed a lack of sealing zones and poor attachment of Osx1Cre.Efnb2 Δ/Δ osteoclasts to growth plate cartilage. Osteoblasts at the growth plate were also poorly attached and impaired in their ability to deposit osteoid. By 6 months of age, trabecular bone mass, osteoclast morphology and osteoid deposition by Osx1Cre.Efnb2 Δ/Δ osteoblasts were normal. Cultured chondrocytes from Osx1Cre. Efnb2 Δ/Δ neonates showed impaired support of osteoclastogenesis but no significant change in Rankl (Tnfsf11) levels, whereas Adamts4 levels were significantly reduced. A population of ADAMTS4 + early hypertrophic chondrocytes seen in controls was absent from Osx1Cre.Efnb2 Δ/Δ neonates. This suggests that Osx1Cre-expressing cells, including hypertrophic chondrocytes, are dependent on ephrin B2 for their production of cartilagedegrading enzymes, including ADAMTS4, and this might be required for attachment of osteoclasts and osteoblasts to the cartilage surface during endochondral ossification.

Retinoic Acid Receptor γ Activity in Mesenchymal Stem Cells Regulates Endochondral Bone, Angiogenesis, and B Lymphopoiesis

“…Intriguingly, Prrx1:Rarg Δ/Δ mice also exhibited islands of hypertrophic chondrocytes trapped in the trabecular bone in the epiphysis of tibias; this also suggests an extension of the hypertrophic stage. Cartilage remnants have similarly been observed in diaphyseal trabecular bone of Osx1‐Cre:EphrinB2 Δ/Δ mice and occur because of defective osteoclastic resorption in the primary ossification center . Similarly, children with osteogenesis imperfecta also contain cartilage within their bones after treatment with antiresorptive bisphosphonate therapy .…”

Inhibition of Axin1 in osteoblast precursor cells leads to defects in postnatal bone growth through suppressing osteoclast formation

“…31 Meanwhile, osteoclasts are also capable of absorbing the mineralized cartilage matrix. 32,33 Mice lacking TRAP resulted in an expanded hypertrophic zone and disordered hypertrophic chondrocyte columns that extended into the trabecular bone region. 34 Mice lacking RANK showed an even more severe phenotype of an expanded hypertrophic zone.…”

Osteoclast depletion with clodronate liposomes delays fracture healing in mice

“…Chondrocytes also can express RANKL and OPG to control osteoclast formation during endochondral ossification . Finally, a recent study suggests that Ephrin B2 expression by chondrocytes is important for promoting osteoclast activity and resolving cartilage during endochondral ossification …”