Cellular interactions and signaling in cartilage development

Abstract

The long bones of the developing skeleton, such as those of the limb, arise from the process of endochondral ossification, where cartilage serves as the initial anlage element and is later replaced by bone. One of the earliest events of embryonic limb development is cellular condensation, whereby pre-cartilage mesenchymal cells aggregate as a result of specific cell-cell interactions, a requisite step in the chondrogenic pathway. In this review an extensive examination of historical and recent literature pertaining to limb development and mesenchymal condensation has been undertaken. Topics reviewed include limb initiation and axial induction, mesenchymal condensation and its regulation by various adhesion molecules, and regulation of chondrocyte differentiation and limb patterning. The complexity of limb development is exemplified by the involvement of multiple growth factors and morphogens such as Wnts, transforming growth factor-beta and fibroblast growth factors, as well as condensation events mediated by both cell-cell (neural cadherin and neural cell adhesion molecule) and cell-matrix adhesion (fibronectin, proteoglycans and collagens), as well as numerous intracellular signaling pathways transduced by integrins, mitogen activated protein kinases, protein kinase C, lipid metabolites and cyclic adenosine monophosphate. Furthermore, information pertaining to limb patterning and the functional importance of Hox genes and various other signaling molecules such as radical fringe, engrailed, Sox-9, and the Hedgehog family is reviewed. The exquisite three-dimensional structure of the vertebrate limb represents the culmination of these highly orchestrated and strictly regulated events. Understanding the development of cartilage should provide insights into mechanisms underlying the biology of both normal and pathologic (e.g. osteoarthritis) adult cartilage.

Isolation and chondroinduction of a dermis‐isolated, aggrecan‐sensitive subpopulation with high chondrogenic potential

“…By using this scaffoldless approach with chondrocytes, we have successfully obtained cartilage-like constructs that mimic native cartilage in terms of biochemical and biomechanical properties. Although the exact mecha-nisms of the self-assembly process initiated and accomplished by chondrocytes are not known, temporal and spatial interactions between the chondrocytes and their ECM environments have been suggested to be essential for successful cartilage development, based on in vivo and in vitro research, as previously reviewed (49). Encouraged by these findings, we were motivated to investigate whether the chondroinduced DIAS cells in 2-D culture could undergo a self-assembly process similar to the one chondrocytes underwent in a 3-D environment.…”

Differentiation of mesenchymal stem cells to osteoblasts and chondrocytes: a focus on adenosine receptors

“…These condensations are characterised as tightly packed cells that express specific condensation markers, and will determine the position, shape and size of the skeletal elements (Ref. 5). The transforming growth factor-β and Hox family of molecules, derived from the epithelium, have been implicated in directing the formation of condensations.…”

“…Runx2 is expressed in prechondrogenic and preosteogenic condensations, but during early embryogenesis, outside signals regulate its expression (Ref. 5). Homeobox protein A2 (Hoxa-2) and Wnt (wingless-type mouse mammary tumor virus (MMTV) integration site) signalling have both been implicated in this process.…”

Epiphyseal growth plate and secondary peripheral chondrosarcoma: the neighbours matter

“…Cells of condensation form a cartilaginous template that is ultimately replaced by bone ( Figure 1). Cell-cell interactions and the transcription factor Sox9 regulate the formation of these condensations [3]. Cell adhesion molecules, such as N-cadherin and N-CAM, are important in establishing an aggregation centre by recruiting mesenchymal cells from surrounding tissue [2].…”

“…Cell adhesion molecules, such as N-cadherin and N-CAM, are important in establishing an aggregation centre by recruiting mesenchymal cells from surrounding tissue [2]. Sox9 plays a key role in the differentiation of progenitor chondrocytes into chondrocytes by modulating the expression of cartilage-specific genes, such as type II and type XI collagen genes [3]. Down-regulation of N-CAM by the binding of syndecan to fibronectin and activation of the typical chondrocyte columns of the growth plate ( Figure 1) [7][8][9].…”