Natural Large-Scale Regeneration of Rib Cartilage in a Mouse Model

Abstract

The clinical need for methods to repair and regenerate large cartilage and bone lesions persists. One way to make new headway is to study skeletal regeneration when it occurs naturally. Cartilage repair is typically slow and incomplete. However, an exception to this observation can be found in the costal cartilages, where complete repair has been reported in humans but the cellular and molecular mechanisms have not yet been characterized. In this study, we establish a novel animal model for cartilage repair using the mouse rib costal cartilage. We then use this model to test the hypothesis that the perichondrium, the dense connective tissue that surrounds the cartilage, is a tissue essential for repair. Our results show that full replacement of the resected cartilage occurs quickly (within 1 to 2 months) and properly differentiates but that repair occurs only in the presence of the perichondrium. We then provide evidence that the rib perichondrium contains a special niche that houses chondrogenic progenitors that possess qualities particularly suited for mediating repair. Label-retaining cells can be found within the perichondrium that can give rise to new chondrocytes. Furthermore, the perichondrium proliferates and thickens during the healing period and when ectopically placed can generate new cartilage. In conclusion, we have successfully established a model for hyaline cartilage repair in the mouse rib, which should be useful for gaining a more detailed understanding of cartilage regeneration and ultimately for developing methods to improve cartilage and bone repair in other parts of the skeleton.

An essential role for IGF2 in cartilage development and glucose metabolism during postnatal long bone growth

“…Second, IGF2 regulates perichondrial cell proliferation and differentiation. Perichondrium is plays a crucial role in long bone elongation by facilitating the PTHrP/Ihh signaling loop as well as providing a source of osteoblasts (Colnot et al, 2004; Derks et al, 2013; Hill et al, 2005;Hojo et al, 2013;Kobayashi et al, 2011;Srour et al, 2015;Van Osch et al, 2000). However, mechanisms to ensure perichondrial cell proliferation and survival during rapid postnatal bone growth are not well understood.…”

“…5E,F). As perichondrial cells can differentiate into osteoblasts and chondrocytes (Colnot et al, 2004;Kobayashi et al, 2011;Srour et al, 2015), the expression of Sox9 and Runx2 was assessed, and a reduction in these two proteins was observed ( Fig. 5G).…”

A Surgical Procedure for Resecting the Mouse Rib: A Model for Large-Scale Long Bone Repair

“…In addition, the contribution of the periosteum to repair can be easily assessed. Futhermore, because the rib has both cartilage and bone segments, comparisons between the healing of these different but related tissue types may identify a common feature of effective repair 18 .…”

Enhanced cartilage repair in ‘healer’ mice—New leads in the search for better clinical options for cartilage repair

“…Srour et al developed a novel animal model for costal cartilage repair where the central cartilage is removed with and without the perichondrium and tested the ability of MRL/MpJ and CD-1 mice to restore costal cartilage [96]. Both strains regenerated costal cartilage within one to two months post-surgery when the perichondrium was left intact, whereas no healing occurred when the perichondrium was removed thus highlighting the importance of the perichondrium in cartilage healing.…”