Sequence of development of innately regenerated growth‐plate cartilage in the hindlimb of the neonatal rat

Abstract

It has long been appreciated that the neonatal rat can regenerate the distal femoral growth-plate. Earlier descriptions of this process pointed to the age of the rodent and level and angle of amputation as significant modifiers of the regeneration process; but none identified the origin of the chondrocytes forming the growth-plate regenerate, nor described the time course and significant milestones of the process. Examination of these issues constitutes the objective of the present report. Fifty-four male, outbred albino rats sustained low femoral (48 rats) or midtibiofibular (six rats) hind-limb amputations when ten to eleven days old. They were killed after 0, 1, 2, 4, 7, 14, 22 or 29 postoperative days; and their amputation stumps were sectioned longitudinally. Twenty-four hr after amputation, the distal femoral periosteum was thickened and metachromatic regions were observed forming within it. Intraperiosteal cartilage was observed by the end of the second postoperative day in four of six limb stumps and, during the following week, expanded considerably in volume. Regenerated growth-plate cell architecture was recognized within the enlarging cartilage mass by the end of the second week; and, by the end of the fourth postoperative week, the regenerating growth-plate region had achieved considerable architectural maturity.

Skeletal callus formation is a nerve‐independent regenerative response to limb amputation in mice and Xenopus

“…On the other hand, the growth of the amputation callus is driven by proliferation of undifferentiated mesenchymal cells, which eventually differentiate into chondrocytes in the callus. Several studies indicate that the growth plate regenerates at the amputated bone terminus in rat neonates (Libbin & Weinstein , ), although we did not find regenerated growth plates in our mouse samples, perhaps because we focused only on the early phase. However, even if the growth plate could regenerate, formation of the amputation callus does not seem to be a result of regeneration of the growth plate because of the difference in cellular contribution between the amputation callus and growth plate.…”

Dynamic changes after murine digit amputation: The MRL mouse digit shows waves of tissue remodeling, growth, and apoptosis

“…Here, limited cartilaginous and dermal blastema‐like growth is seen. This is also seen in electrically‐stimulated tissue 15 and in the very young rat 40 …”

“…In conclusion, digit regrowth in adult B6 and SW mice is very similar to that seen in studies of limb regeneration in the rat with little evidence of tissue growth. 40 On the other hand, the MRL mouse has some similarities to what is seen in the rat after limb amputation when adjacent muscle is still present. Here, limited cartilaginous and dermal blastema-like growth is seen.…”

“…This is also seen in electricallystimulated tissue 15 and in the very young rat. 40 Collectively, the presence of a proliferating cell mass, basement membrane breakdown, collagen deposition, complete and early reepithelialization, and an ongoing apoptotic response is suggestive of a regenerating blastemalike structure unique to the MRL mouse.…”

Integrating levels of bone growth control: From stem cells to body proportions

“…With regards to bone growth, while external recruitment does not seem to play a major role during normal development, this contribution could very well increase during catch‐up growth after injury or perturbation, as recent studies have suggested that injury‐induced changes in the microenvironment can activate a distinct stem cell population involved in repair (Chan et al, 2015; Marecic et al, 2015; Worthley et al, 2015). Moreover, classic studies showed partial regeneration of the GP after bone amputation (Libbin & Weinstein, 1986, 1987), suggesting that cells previously intended for a different fate are redirected to compensate for injury. Support for this notion can be seen in studies that found that co‐delivery of BMP2 and VEGF inhibitors can redirect adipose tissue to chondroprogenitor fate, suggesting the mechanism exists already in part (Chan et al, 2015; Zhou et al, 2014).…”