“Tissue Induction”
At a Glance
Section titled “At a Glance”| Metadata | Details |
|---|---|
| Publication Date | 2025-07-07 |
| Journal | South African Dental Journal |
| Authors | Ugo Ripamonti |
| Institutions | University of the Witwatersrand |
Abstract
Section titled “Abstract”This contribution to the induction of tissue formation starts with seemingly simple questions, “Why Bone?” and “Why Cartilage?”, the essential ingredients to compose the skeleton ad thus the speciation of the vertebrates, the induction of long bone via endochondral ossification, the induction of the growth plate, body erection and the speciation thus of the Homo clade, walking upright toward the spectacular creativity of extant Homo sapiens. The title wishes to pay tribute to grand pioneer scientists such as Pollettini, Levander, Moss, Urist and Reddi who persevered to study the induction of bone formation as initiated by devitalized demineralized bone matrices. “Tissue Induction” is the title of a seminal paper by Gustav Levander in Nature, 1945. Levander hypothesized that unknown substances from heterotopically implanted bone matrices would activate recipient resident cells to initiate the induction of bone formation, where there is no bone. Levander went further by using the term “Tissue Induction” linking the induction of bone formation to embryonal development as described by Hans Spemann and Hilde Mangold, the 1935 Nobel Prize for Medicine and Physiology. Phylogenetically, bones were an ancestral character, and cartilage developed later, providing the growth plate, to growth vertebrate’ long bones establishing body erection in selected hominid’ clades. The TGF-β supergene family includes several osteogenic proteins endowed with the remarkable capacity to initiate the heterotopic induction of bone. Besides the sub-family of the bone morphogenetic proteins (BMPs), in primates and in primates only, the three mammalian TGF-β isoforms also initiate the induction of bone formation. Heterotopic implantation of recombinant hTGF-β3 initiates the induction of bone formation by priming resident intramuscular cells, pericytes, myoendothelial cells and myoblastic cells to express and secrete BMPs genes and gene products; the expression and synthesis of BMPs initiate the induction of bone formation regulated by Noggin expression. Combined morphological and molecular analyses have indicated that doses of hTGF-β3 in Matrigel®Matrix set into motion the in vivo development of multiple tissues and multicellular organoids within the implanted furcation bioreactors. Organoids form by gene expression pathways from available different cellular populations within the exposed furcation bioreactor. Our molecular and morphological data using undecalcified whole mounted sections cut by the Exakt diamond saw technique have indicated that hTGF-β3 in Matrigel®Matrix induces distinct supracellular phases that together with morphological transformation and organogenesis result in the generation of intramuscular mineralized bone organoids.