page_title: Mechanotransduction
section_title: Cartilage
hierarchical_section_title: Mechanotransduction / Cartilage
caption_attribution_description: From en:Gray's Anatomy.
context_page_description: Mechanotransduction is any of various mechanisms by which cells convert mechanical stimulus into electrochemical activity. This form of sensory transduction is responsible for a number of senses and physiological processes in the body, including proprioception, touch, balance, and hearing. The basic mechanism of mechanotransduction involves converting mechanical signals into electrical or chemical signals.
  In this process, a mechanically gated ion channel makes it possible for sound, pressure, or movement to cause a change in the excitability of specialized sensory cells and sensory neurons. The stimulation of a mechanoreceptor causes mechanically sensitive ion channels to open and produce a transduction current that changes the membrane potential of the cell. Typically the mechanical stimulus gets filtered in the conveying medium before reaching the site of mechanotransduction. Cellular responses to mechanotransduction are variable and give rise to a variety of changes and sensations. Broader issues involved include molecular biomechanics.
context_section_description: One of the main mechanical functions of articular cartilage is to act as a low-friction, load-bearing surface.  Due to its unique location at joint surfaces, articular cartilage experiences a range of static and dynamic forces that include shear, compression and tension. These mechanical loads are absorbed by the cartilage extracellular matrix (ECM), where they are subsequently dissipated and transmitted to chondrocytes (cartilage cells).
  Chondrocytes sense and convert the mechanical signals they receive into biochemical signals, which subsequently direct and mediate both anabolic (matrix building) and catabolic (matrix degrading) processes.  These processes include the synthesis of matrix proteins (type II collagen and proteoglycans), proteases, protease inhibitors, transcription factors, cytokines and growth factors.
  The balance that is struck between anabolic and catabolic processes is strongly influenced by the type of loading that cartilage experiences.  High strain rates (such as which occurs during impact loading) cause tissue damage, degradation, decreased matrix production and apoptosis. Decreased mechanical loading over long periods, such as during extended bed-rest, causes a loss of matrix production. Static loads have been shown to be detrimental to biosynthesis while oscillatory loads at low frequencies (similar that of a normal walking gait) have been shown to be beneficial in maintaining health and increasing matrix synthesis. Due to the complexity of in-vivo loading conditions and the interplay of other mechanical and biochemical factors, the question of what an optimal loading regimen may be or whether one exists remain unanswered.
  Although studies have shown that, like most biological tissues, cartilage is capable of mechanotransduction, the precise mechanisms by which this is done remain unknown.  However, there exist a few hypotheses which begin with the identification of mechanoreceptors.
  In order for mechanical signals to be sensed, there need to be mechanoreceptors on the surface of chondrocytes.  Candidates for chondrocyte mechanoreceptors include stretch-activated ion channels (SAC), the hyaluronan receptor CD44, annexin V (a collagen type II receptor), and integrin receptors (of which there exist several types on chondrocytes).
  Using the integrin-linked mechanotransduction pathway as an example (being one of the better studied pathways), it has been shown to mediate chondrocyte adhesion to cartilage surfaces, mediate survival signaling and regulate matrix production and degradation.
  Integrin receptors have an extracellular domain that binds to the ECM proteins (collagen, fibronectin, laminin, vitronectin and osteopontin), and a cytoplasmic domain that interacts with intracellular signaling molecules.  When an integrin receptor binds to its ECM ligand and is activated, additional integrins cluster around the activated site.  In addition, kinases (e.g., focal adhesion kinase, FAK) and adapter proteins (e.g., paxillin, Pax, talin, Tal and Shc) are recruited to this cluster, which is called the focal adhesion complex (FAC).  The activation of these FAC molecules in turn, triggers downstream events that up-regulate and /or down-regulate intracellular processes such as transcription factor activation and gene regulation resulting in apoptosis or differentiation.
  In addition to binding to ECM ligands, integrins are also receptive to autocrine and paracrine signals such as growth factors in the TGF-beta family.  Chondrocytes have been shown to secrete TGF-b, and upregulate TGF-b receptors in response to mechanical stimulation; this secretion may be a mechanism for autocrine signal amplification within the tissue.
  Integrin signaling is just one example of multiple pathways that are activated when cartilage is loaded.  Some intracellular processes that have been observed to occur within these pathways include phosphorylation of ERK1/2, p38 MAPK, and SAPK/ERK kinase-1 (SEK-1) of the JNK pathway as well as changes in cAMP levels, actin re-organization and changes in the expression of genes which regulate ca
caption: Cartilage experience tension, compression and shear forces in vivo
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