| Popis: |
As a unique connective tissue, cartilage is made of only one cell type, chondrocytes, and their secreted extracellular matrix (ECM), of which the most abundant are type II collagen and proteoglycans. Despite its simple cell composition, cartilage as a tissue is quite heterogenic and varies in origin, structure, matrix proteins, developmental and physiological roles. While in some invertebrates, such as cartilaginous fish (elasmobranches) like sharks, cartilage tissues are permanent in order to support the major organs of the body, most cartilage tissues in vertebrates have only a temporary existence, serving as a template for the arising bony skeleton via a highly spatiotemporally regulated process termed “endochondral ossification.” This type of mechanism is responsible for the formation of all long bones of the axial skeleton (vertebrae and ribs) and the appendicular skeleton (limbs). During this process, mesenchymal progenitor cells first move to the future bone sites and then differentiate into chondrocytes to form a cartilage anlage. Next, chondrocytes undergo sequential stages of proliferation, prehypertrophy, hypertrophy, and finally mineralization. Eventually the terminally differentiated chondrocytes, along with their surrounding cartilage matrix, have to be removed and replaced by bone matrix produced by osteoblasts. In adults, bone fracture healing adopts a similar mechanism. During repair, an initial soft cartilage callus is later replaced by a hard, bony callus for further remodeling into cortical bone. Not all chondrocytes differentiate unidirectionally. At the cartilage anlage stage of development, chondrocytes at future joint sites undergo de-differentiation to mesenchymal progenitors and then re-differentiate into multiple joint tissues, including cartilage chondrocytes. Recently, the fate of terminally differentiated chondrocytes has become controversial. Instead of apoptosis, as suggested by the conventional view, more and more evidence demonstrates that some hypertrophic chondrocytes undergo transdifferentiation into osteogenic lineage cells. In this article, we present the up-to-date knowledge about how chondrocytes in transient cartilage are formed, differentiated, and eventually removed during skeletal development and repair, with a focus on regulatory transcription factors and growth factors. We use the hindlimb as a primary example but the mechanisms also apply to other long bones. |
