Orientation of Primary Cilia of Articular Chondrocytes in Three‐Dimensional Space

Abstract

Primary cilia have functions as sensory organelles integral to signal transduction and establishment of cell polarity. In articular cartilage the primary cilium has been hypothesized to function as an antenna to sense the biomechanical environment, regulate the secretion of extracellular matrix components, and maintain cellular positional information, leading to high tissue anisotropy. We used analysis of electron microscopy serial sections to demonstrate positional attributes of the primary cilium of adult equine articular chondrocytes in situ. Data for $500 axonemes, comparing superficial to radiate chondrocytes from both load-bearing and non-load-bearing regions, were graphed using spherical co-ordinates y, u. The data demonstrate the axoneme has a definable orientation in 3D space differing in superficial and radiate zone chondrocytes, cells that differ by 90 in the orientation of their major axes to the articular surface. Axonemal orientation is more definable in load-bearing than in non-loadbearing areas. The position of emergence of the axoneme from the cell also is variable. In load-bearing regions of the superficial zone, extension of the axoneme is from the cellular side facing the subchondral bone. In radiate zone cells, axonemes extend from either face of the chondrocyte, that is, both toward the articular surface or toward the subchondral bone. In non-load-bearing regions this consistency is lost. These observations relate to current hypotheses concerning establishment of tissue anisotropy in articular cartilage during development, involving both migration of cells from the joint periphery and a restricted zone of division within the tissue resulting in the columnar arrangement of radiate zone cells. Anat Rec, 294:533-549, 2011. V V C 2011 Wiley-Liss, Inc.

Depletion of primary cilia in articular chondrocytes results in reduced Gli3 repressor to activator ratio, increased Hedgehog signaling, and symptoms of early osteoarthritis

“…A role for chondrocyte primary cilia in sensing mechanical signals has been proposed by observations of cilia orientation and projection within the cartilage matrix [13, 35–38]. In articular cartilage, primary cilia in the superficial layer point away from the articular surface while primary cilia on chondrocytes in the mid or deep zone of load bearing joints can be pointed towards the articular surface or towards the subchondral bone [37]. Orientation is not consistent in non-load bearing cartilages.…”

Centrosome positioning in vertebrate development

“…Cilia are oriented in chondrocytes relative to the cartilage layer (Farnum and Wilsman, 2011) and in vascular smooth muscle cells relative to the direction of stress (Lu et al, 2008). These directed orientations presumably allow mechanosensory cilia to respond to strains in particular directions.…”

Primary cilia and coordination of receptor tyrosine kinase (RTK) signalling

“…Since Integrins, Notch receptors and several members of GPCRs in Hh and Wnt signalling, as well as neurotransmission, are localized to primary cilia, it is tempting to speculate that ample signalling crosstalk and networking takes place in the cilium–centrosome axis. In connective, muscle and skeletal tissues, the cilium may directly interact with multiple components of ECM to regulate the length and orientation of primary cilia to control cellular positional information [52,81,100,116-119] and, when defective in chondrocytes, may lead to osteoarthritis [120] and osteochondroma [121]. In this regard, the further crosstalk with TRP ion channels, such as polycystins, adds an additional layer of complexity in signalling networking in ciliary mechanosensation [122].…”