Proliferating Cells in Knee Epiphyses of Lizards Allow for Somatic Growth and Regeneration after Damage

Abstract

After bone damage, fracture or amputation, lizards regenerate a variable mass of cartilaginous and fibro-cartilaginous tissues, depending from the anatomical site and intensity of inflammation. Aside tail and vertebrae, also long bones and knee epiphyses can regenerate a relative large mass of cartilage after injury. Regeneration is likely related to the persistence of stem cells in growing centers of these bones, localized in the epiphyses of femur, tibia and fibula. The epiphyses form ossified secondary centers in adults but a few progenitor cells remain in the articular cartilage and growth plate, allowing a continuous growth during most lifetime of lizards. The present Review indicates that putative progenitor/stem cells, identified by long labeling retaining of 5-bromo-deoxy-uridine (5BrdU) and immunolocalization of telomerase, remain localized in the articular cartilage and growth plates of the femur and tibia. These cells are re-activated after limited epiphyses damage or amputation of the distal part of the femur or tibia-fibula, and can re-form cartilaginous epiphyses. Regenerating chondrocytes show an intense proliferation and the production of new extracellular matrix components such as collagen VI, chondroitin sulfate proteoglycan, and hyaluronate receptors. The molecular factors at the origin of the chondrogenic potential of the articular cartilage, growth plates, and the periosteum in lizard bones remain to be studied.

Tail regeneration in Lepidosauria as an exception to the generalized lack of organ regeneration in amniotes

“…Epiphyses of knees in adult lizards, containing large secondary ossification centers like in mammals, can regenerate a variable amount of cartilage. Epiphyses contain residual cartilage cells on the articular surface that surround the secondary cavities hosting bone marrow and bony trabeculae (Figure 8a; Alibardi, 2015e, 2015f, 2017c). After damaging the knee with deep incisions/wounds in the lizard P. muralis , within the first week postdamage an initial degeneration of chondrocytes, bone cells, and ligaments occurs on both the articular surfaces (Figure 8b).…”