Osteoarthritis pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohammadmain Rezazadehsaatlou [2], Irfan Dotani [3]
Overview
Osteoarthritis (OA) is a well-known degenerative joint disease influencing millions of people worldwide. Osteoarthritis is a complex disease caused by changes in the tissues' homeostasis of articular cartilages and subchondral bones. The cell/extracellular matrix (ECM) and their interactions play an important role in the pathophysiology of articular cartilage and the occurrence of Osteoarthritis. Consequently, the main feature of OA is that after this process is involved, the articular cartilages of the involved joint no longer will have a normal acting system because the destruction of the articular cartilages can no longer act as shock absorber.
Pathophysiology
Different pathogenic mechanisms have been proposed to be responsible for the occurrence of OA. Heredity, obesity, hypoxia, synovitis–capsulitissubchondral bone overload, joint instability (mechanical integrity disturbances) are the most important underlying causes in this regard. In the current pathogenesis of osteoarthritis (OA), all joint tissues including cartilage, bone, synovium, ligamentous capsular structures, and surrounding muscle are involved. OA is characterized by structural changes such as active bone remodeling, synovial inflammation, and articular cartilage degradation leading to the loss of joint function and angular deformity or malalignment. Also, a variety of biomarkers in synovial fluid have helped to create more clear insight into the biological response of joints to injury. However, no biomarker has been declared to be reliable for monitoring the development, progression, and response to therapy of OA. Its been reported that certain factors can increase the risk of the OA development such as hereditary elements, trauma and mechanical stress, joint injury, age, obesity, physical activity, bone mineral density (BMD), and congenital anomalies. During the last years, signaling pathways have drawn a lot of attention and proven that these pathways play important roles in inflammation and in the remodeling of the subchondral bone, synovium, enzyme activation, and extracellular matrix degradation in articular cartilage [1] [2] [3][4].
Subchondral Bone
OA leads to the sub-chondral bone remodeling. This event is often along with the sub-chondral cysts formation as a result of focal resorption. OA can alter chondrocyte metabolism in bony cells. Osteoarthritis, influencing whole joint systems, includes both articular cartilage and underlying bone structures. One of the most common findings in OA is the subchondral bone plate thickening. The diseased bone becomes brittle and sclerotic, and the frequent turnovers affect bone quality. There is still controversy about whether the subchondral bone change happens simultaneously with the changes in articular cartilage or not. Articular overgrowths such as subchondral bone lead to microtrauma, hardening, remodeling, and displacement of the osteochondral line. Consequently, the energy-dissipation capacity and elasticity of the articular cartilage decrease. Macroscopic changes of the subchondral bone especially in load-bearing areas are increased osteogenetic reactions, increased stiffness, increased density, and excessive formation of bone and cartilage (called osteochondrophytes). OA is also capable of influencing the non–weight-bearing joints, such as hands, spine, shoulders, and temporomandibular joints. The osteochondrophytes usually can be found in intra-articular, marginal, extraarticular, insertional, or enthesiophytes. The osteochondrophytes frequently involves the joint space, and with synovial metaplastic fragments or flaps of cartilage, they lead to the articular ‘joint mice’ formation. On the other hand, the bone remodeling caused by microfractures within the superficial bone trabeculae with the formation of subchondral bone cysts (known as erosive alterations). Bony changes such as sclerosis of the subchondral bone plate, alterations in trabecular structure, osteophytes and bone marrow lesions are associated with the initiation and progression of OA. It’s been reported that the subchondral bone changes prior to the articular cartilage changes. Meanwhile, it’s been found that the molecular pathways (for example, cytokines such as IL-1, TNF-α, fibrinolytic system including plasminogen, tissue plasminogen activators, urokinase plasminogen activators, and plasmin) have in subchondral play important roles in the disbalance between the physiological connection of bone deposition and remodeling and resorption potential. Higher osteoblastic activity results in an exaggerated reparative response. In contrast, an increased osteoclastic degradative activity results in a predominantly erosive bony condition[5][6][7][8][9][10][11].
Articular Cartilage
The articular cartilage damage is one of the most important pathological causes of OA. It is not clear whether this pathological event originates from the cartilage or subchondral bone, loss and/or damage to articular cartilage or both of them are responsible for the development and progression of OA. Human articular cartilage system, acting as a shock absorber, consists of a hydrated extracellular matrix (as the functional elements of the tissue) with few numbers of chondrocytes within. 70–80% of cartilage consists of water and collagens and proteoglycans are the major organic components. Collagen type II builds a network of fibers containing molecules within. Collagen type XI helps collagen type II in fibril network formation and also limiting the fiber diameter. Collagen type IX make crosslinks the whole collagen network. Heparan sulfate proteoglycans such as perlecan, have important roles (such as interactions with heparin-binding growth factors like fibroblast growth factors, heparin binding forms of vascular endothelial growth factor (VEGF), and bone morphogenetic proteins (BMP)) in chondrogenesis. Higher demolition of heparan sulfate proteoglycans by glycosidases and matrix metalloproteinases are known to responsible for OA. Calcification and ossification in articular cartilage during OA and aging occurs due to the differentiation of chondrocytes. During the degenerative changes in involved joints, calcification happens simultaneously with to increasing alkaline phosphates and pyrophosphate levels. Since the Articular cartilage has no internal vascular or lymphatic supply system so it is dependent on near tissues including subchondral bone and synovial membrane in receiving nutrients elements and excretion of products of made by articular matrix turnover and chondrocyte metabolism [12][13][1][9][14][15][16].
Synovial Membrane
The main task of Synovial Membrane is repairing any defects found in joint. The cellular compartment of the synovial membrane of the SM is a major source of synovial fluid. These components are responsible for management of chondrocyte activities and maintaining the integrity of articular cartilage surfaces (using lubricin and hyaluronic acid molecules) in diarthrodial joints. After a joint injury, the concentration of this molecular system changes. During the progression of OA, this synovial membrane changes into the main origin of proinflammatory and catabolic products such as metalloproteinases and aggrecanases. Thus, any damage to the synovial membrane can result in reducing of cartilage-protecting factors, and also an increase in production of articular matrix degradation factors. A normal synovial membrane has full control on the transmitted molecules in and out of the joint space. During some conditions such as trauma, inflammation, and OA this permeability of synovial membrane disrupts leading to reduced concentrations of lubricin and hyaluronic acid[17][18][19][20]._and_complement_activation_(b)_in_the_joint_leading_to_synovitis_and_potentiation_of_cartilage_erosion_in_OA.jpg)
Joint Instability
Joint instability occurs due to the ligament laxity enhancement, poor muscles conditions, or ligament tearing or strain in a ligament or abnormal muscles status. Joint instability increases the incidence of OA. Joint instability could be found as a result of synovitis produces excessive amounts of synovial fluid[21][22].
Hypoxia
Neovascularization in synovial membrane, subchondral bone, and cartilage is a common finding in OA. Neovascularization in the injured area increases the nutrients delivery of to the stressed articular cartilage and subchondral and also could cause the synovitis development in bone. Hypoxia as a common pathophysiological element of OA and rheumatoid arthritis because during OA, cartilage thinning and cartilage erosion, ECM composition changes, and the cartilage fissures development are the most common findings in involved joint. These structural alteration influence the oxygen gradient near the articular cartilage. In OA and rheumatoid arthritis, the two important angiogenic peptides including vascular endothelial growth factor and platelet-derived cellular endothelial growth factor. The increases due to the excessive expression of nuclear hypoxia-inducible factors. These angiogenic peptides increase local neovascularization and increase vascular permeability, consequently causing inflammation, cartilage damage, edema, and protein vascular leak that worsen the joint involvement [23][24].
References
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- ↑ Wise BL, Niu J, Yang M, Lane NE, Harvey W, Felson DT, Hietpas J, Nevitt M, Sharma L, Torner J, Lewis CE, Zhang Y (June 2012). "Patterns of compartment involvement in tibiofemoral osteoarthritis in men and women and in whites and African Americans". Arthritis Care Res (Hoboken). 64 (6): 847–52. doi:10.1002/acr.21606. PMC 3340516. PMID 22238208.
- ↑ Andriacchi TP, Koo S, Scanlan SF (February 2009). "Gait mechanics influence healthy cartilage morphology and osteoarthritis of the knee". J Bone Joint Surg Am. 91 Suppl 1: 95–101. doi:10.2106/JBJS.H.01408. PMC 2663350. PMID 19182033.
- ↑ Haq I, Murphy E, Dacre J (July 2003). "Osteoarthritis". Postgrad Med J. 79 (933): 377–83. PMC 1742743. PMID 12897215.
- ↑ Stone L (November 2008). "Aches, pains and osteoarthritis". Aust Fam Physician. 37 (11): 912–7. PMID 19037464.
- ↑ Dieppe PA, Lohmander LS (2005). "Pathogenesis and management of pain in osteoarthritis". Lancet. 365 (9463): 965–73. doi:10.1016/S0140-6736(05)71086-2. PMID 15766999.
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- ↑ 9.0 9.1 Dimitroulas T, Duarte RV, Behura A, Kitas GD, Raphael JH (October 2014). "Neuropathic pain in osteoarthritis: a review of pathophysiological mechanisms and implications for treatment". Semin. Arthritis Rheum. 44 (2): 145–54. doi:10.1016/j.semarthrit.2014.05.011. PMID 24928208.
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- ↑ Henrotin Y, Pesesse L, Sanchez C (2009). "Subchondral bone in osteoarthritis physiopathology: state-of-the art and perspectives". Biomed Mater Eng. 19 (4–5): 311–6. doi:10.3233/BME-2009-0596. PMID 20042798.
- ↑ Mortellaro CM (September 2003). "Pathophysiology of osteoarthritis". Vet. Res. Commun. 27 Suppl 1: 75–8. PMID 14535372.
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- ↑ Funck-Brentano T, Cohen-Solal M (July 2015). "Subchondral bone and osteoarthritis". Curr Opin Rheumatol. 27 (4): 420–6. doi:10.1097/BOR.0000000000000181. PMID 26002035.
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