The skeleton provides a rigid, protective frame for the rest of the body and large injuries or defects can be incapacitating. In particular, the treatment f segmental defects remains an unresolved problem today. Autogenous bone graft is limited in supply and the biological activity of bone graft substitutes requires further refinement. Thus, new strategies for more physiological healing of critical sized bone defects are much needed. Studying models for bone regeneration in small mammals is a vital first step to developing treatments for severe skeletal injuries. Although humans do not repair as well as amphibians, human adults demonstrate a remarkable ability to regenerate large portions of the rib (>6 inches). We have developed a mouse model for rib repair that is amenable to genetic and surgical manipulation. Our preliminary studies have shown that 1) complete repair occurs within 1-2 months, 2) regrowth occurs in the middle of the resection site as well as from the ends, and 3), that the presence of the surrounding connective tissue sheath, or periosteum, is required for complete healing to occur. Based on our preliminary findings we now aim 1) to determine what steps occur to build new bone with the expectation that a rapidly produced cartilage intermediate is key and 2) to determine if the cells involved in the repair arise from progenitors in the periosteum. Our ultimate goal is to harness the unique features of rib skeletal repair to develop methods for enhancing bone healing in other locations of the body.
Humans do not repair large skeletal defects with the exception of the ribs, where large segments of both the cartilage and bone portions can be removed followed by complete regeneration. To analyze the cellular and molecular pathways required in both cartilage and bone repair within this context, we have established a rib skeletal regeneration model in the mouse. Ultimately the long-term goal would be to progressively translate our findings to more stringent models in order to develop a skeletal repair strategy that can be evaluated in patients.
|Paul, Sandeep; Schindler, Simone; Giovannone, Dion et al. (2016) Ihha induces hybrid cartilage-bone cells during zebrafish jawbone regeneration. Development 143:2066-76|
|Srour, Marissa K; Fogel, Jennifer L; Yamaguchi, Kent T et al. (2015) Natural large-scale regeneration of rib cartilage in a mouse model. J Bone Miner Res 30:297-308|
|Tripuraneni, Nikita; Srour, Marissa K; Funnell, John W et al. (2015) A surgical procedure for resecting the mouse rib: a model for large-scale long bone repair. J Vis Exp :52375|