Mechanoadaptation: articular cartilage through thick and thin

Abstract

The articular cartilage is exquisitely sensitive to mechanical load. Its structure is largely defined by the mechanical environment and destruction in osteoarthritis is the pathophysiological consequence of abnormal mechanics. It is often overlooked that disuse of joints causes profound loss of volume in the articular cartilage, a clinical observation first described in polio patients and stroke victims. Through the 1980s, the results of studies exploiting experimental joint immobilisation supported this. Importantly, this substantial body of work was also the first to describe metabolic changes that resulted in decreased synthesis of matrix molecules, especially sulfated proteoglycans. The molecular mechanisms that underlie disuse atrophy are poorly understood despite the identification of multiple mechanosensing mechanisms in cartilage. Moreover, there has been a tendency to equate cartilage loss with osteoarthritic degeneration. Here, we review the historic literature and clarify the structural, metabolic and clinical features that clearly distinguish cartilage loss due to disuse atrophy and those due to osteoarthritis. We speculate on the molecular sensing pathways in cartilage that may be responsible for cartilage mechanoadaptation.

The ciliary protein IFT88 controls post-natal cartilage thickness and influences development of osteoarthritis

“…Thinning, ~10% on average, of articular cartilage was most marked on the medial plateau. We speculate this effect is largest on the thicker medial plateau, as thickness is mechanically defined [6], in a manner perhaps analogous to the bone 'mechanostat' proposed by Frost in 1987 [41] and designed to ensure chondrocytes experience forces in a narrow window [1]. The recovery of medial thinning in response to exercise, is conducive with, but does not prove, the possibility that ciliary IFT88 is a component of the cartilaginous response to mechanical inputs and important to adolescent and adult mechanoadaptation, as proposed first in the context of epithelial response to renal flow [14,42], aberrant in polycystic kidney disease [43].…”

“…Physiological mechanical loading has long been established to be critical for cartilage development and homeostasis [4]. Loss of mechanical load leads to thinning (atrophy) of cartilage [5,6]. Pathological, supraphysiological mechanical loading predisposes to the development of osteoarthritis (OA), where degradation of the cartilage occurs with loss of integrity of the articular surface [6].…”

The molecular profile of synovial fluid changes upon joint distraction and is associated with clinical response in knee osteoarthritis

“…The clinical outcome variable was change in KOOS 4 over time (KOOS 4 at either 3, 6 or 12 months respectivelyÀKOOS 4 at baseline). Linear regression was employed to model the relationship between continuous change in analyte levels (concentrations at 6 or 3 weeks e baseline concentrations) and change in KOOS 4 .…”

Human articular cartilage mechanosensitivity is related to histological degeneration – a functional MRI study

“…Articular cartilage is an exquisitely mechanosensitive tissue and its structure and composition are defined by the mechanical environment 1 . Cartilage degeneration, i.e., the hallmark change of osteoarthritis (OA), is considered the consequence of abnormal tissue remodelling processes driven by inflammation, unfavourable biomechanical conditions and predisposing tissue susceptibility 2 .…”