Osteoarthritis: A disease of the joint as an organ

Loeser, Richard F.; Goldring, Steven R.; Scanzello, Carla R.; Goldring, Mary B.

doi:10.1002/art.34453

Cited by 2,372 publications

(2,122 citation statements)

References 97 publications

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“…These alterations are responsible for pain, joint failure, and loss of joint architectural integrity. Current treatments for OA are limited to pain management and, in the late phase of the disease process, joint‐replacement surgery (Loeser, Goldring, Scanzello & Goldring, 2012). There are two major forms of OA.…”

Section: Introductionmentioning

confidence: 99%

Evidence that miR‐146a attenuates aging‐ and trauma‐induced osteoarthritis by inhibiting Notch1, IL‐6, and IL‐1 mediated catabolism

Guan

Yang

et al. 2018

Aging Cell

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SummaryPrimary osteoarthritis (OA) is associated with aging, while post‐traumatic OA (PTOA) is associated with mechanical injury and inflammation. It is not clear whether the two types of osteoarthritis share common mechanisms. We found that miR‐146a, a microRNA‐associated with inflammation, is activated by cyclic load in the physiological range but suppressed by mechanical overload in human articular chondrocytes. Furthermore, miR‐146a expression is decreased in the OA lesions of human articular cartilage. To understand the role of miR‐146a in osteoarthritis, we systemically characterized mice in which miR‐146a is either deficient in whole body or overexpressed in chondrogenic cells specifically. miR‐146a‐deficient mice develop early onset of OA characterized by cartilage degeneration, synovitis, and osteophytes. Conversely, miR‐146a chondrogenic overexpressing mice are resistant to aging‐associated OA. Loss of miR‐146a exacerbates articular cartilage degeneration during PTOA, while chondrogenic overexpression of miR‐146a inhibits PTOA. Thus, miR‐146a inhibits both OA and PTOA in mice, suggesting a common protective mechanism initiated by miR‐146a. miR‐146a suppresses IL‐1β of catabolic factors, and we provide evidence that miR‐146a directly inhibits Notch1 expression. Therefore, such inhibition of Notch1 may explain suppression of inflammatory mediators by miR‐146a. Chondrogenic overexpression of miR‐146a or intra‐articular administration of a Notch1 inhibitor alleviates IL‐1β‐induced catabolism and rescues joint degeneration in miR‐146a‐deficient mice, suggesting that miR‐146a is sufficient to protect OA pathogenesis by inhibiting Notch signaling in the joint. Thus, miR‐146a may be used to counter both aging‐associated OA and mechanical injury‐/inflammation‐induced PTOA.

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Section: Introductionmentioning

confidence: 99%

Evidence that miR‐146a attenuates aging‐ and trauma‐induced osteoarthritis by inhibiting Notch1, IL‐6, and IL‐1 mediated catabolism

Guan

Yang

et al. 2018

Aging Cell

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“…Although successful subtalar joint arthrodesis provides pain relief, resultant alterations in ankle biomechanics need to be considered carefully given the possibility that this procedure may predispose the remaining hindfoot and ankle to accelerated degenerative changes [8,19,21,23,25]. The clinical association among subtalar joint arthrodesis, double (subtalar and talonavicular), and triple (subtalar, talonavicular, and calcaneocuboid) arthrodeses with progressive ankle degeneration is evident in medium-to long-term clinical studies [13,18,24].…”

Section: Introductionmentioning

confidence: 99%

How Do Hindfoot Fusions Affect Ankle Biomechanics: A Cadaver Model

Hutchinson

Baxter

Gilbert

et al. 2016

Clinical Orthopaedics &Amp; Related Research

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Background While successful subtalar joint arthrodesis provides pain relief, resultant alterations in ankle biomechanics need to be considered, as this procedure may predispose the remaining hindfoot and tibiotalar joint to accelerated degenerative changes. However, the biomechanical consequences of isolated subtalar joint arthrodesis and additive fusions of the Chopart's joints on tibiotalar joint biomechanics remain poorly understood. Questions/purposes We asked: What is the effect of isolated subtalar fusion and sequential Chopart's joint fusions of the talonavicular and calcaneocuboid joints on tibiotalar joint (1) mechanics and (2) kinematics during loading for neutral, inverted, and everted orientations of the foot? Methods We evaluated the total force, contact area, and the magnitude and distribution of the contact stress on the articular surface of the talar dome, while simultaneously tracking the position of the talus relative to the tibia during loading in seven fresh-frozen cadaver feet. Each foot was loaded in the unfused, intact control condition followed by three randomized simulated hindfoot arthrodesis modalities: subtalar, double (subtalar and talonavicular), and triple (subtalar, talonavicular, and calcaneocuboid) arthrodesis. The intact and arthrodesis conditions were tested in three alignments using a metallic wedge insert: neutral (flat), 10°i nverted, and 10°everted. Results Tibiotalar mechanics (total force and contact area) and kinematics (external rotation) differed owing to hindfoot arthrodeses. After subtalar arthrodesis, there were Each author certifies that he or she, or a member of their immediate family, has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. Clinical Orthopaedics and Related Research ®A Publication of The Association of Bone and Joint Surgeons® decreases in total force (445 ± 142 N, 95% CI, 340-550 N, versus 588 ± 118 N, 95% CI, 500-676 N; p \ 0.001) and contact area (282 mm 2 , 95% CI, 222-342 mm 2 , versus 336 ± 96 mm 2 , 95% CI, 265-407 mm 2 ; p \ 0.026) detected during loading in the neutral position; these changes also were seen in the everted foot position. Hindfoot arthrodesis also was associated with increased external rotation of the tibiotalar joint during loading: subtalar arthrodesis in the neutral loading position (3.3°± 1.6°; 95% CI, 2°-4.6°; p = 0.004) and everted loading position (4.8°± 2.6°; 95% CI, 2.7°-6.8°; p = 0.043); double arthrodesis in neutral (4.4°± 2°; 95% CI, 2.8°-6°; p = 0.003) and inverted positions (5.8°± 2.6°; 95% CI, 3.7°-7.9°; p = 0.002), and triple arthrodesis in all loaded orientations including neutral (4.5°±1.8°; 95% CI, 3.1°-5.9°; p = 0.002), inverted (6.4°± 3.5°; 95% CI, 3.6°-9.2°; p = 0.009), and everted (3.6°± 2°; 95% CI, 2°-5.2°; p = 0.053) positions. Finally, after subtalar arthrodesis, additive fusions at Chopart's joints did not appear to result in additional observe...

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“…The editorial highlights the general preoccupation of OA research to focus heavily on articular cartilage. This is contrasted with the generally accepted view that OA is not a disorder of cartilage but is a complex condition in which multiple joint tissues are affected (2,3). Based on what I have observed in the published literature, this view of OA is not contested by investigators reporting on cartilage research, which suggests that they are aware that their focus is on one part of the pathology.…”

Section: To the Editormentioning

confidence: 77%

Extending the Paradigm of Osteoarthritis: Comment on the Editorial by McAlindon

Hardingham

2016

Arthritis & Rheumatology

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Osteoarthritis: A disease of the joint as an organ

Cited by 2,372 publications

References 97 publications

Evidence that miR‐146a attenuates aging‐ and trauma‐induced osteoarthritis by inhibiting Notch1, IL‐6, and IL‐1 mediated catabolism

Evidence that miR‐146a attenuates aging‐ and trauma‐induced osteoarthritis by inhibiting Notch1, IL‐6, and IL‐1 mediated catabolism

How Do Hindfoot Fusions Affect Ankle Biomechanics: A Cadaver Model

Extending the Paradigm of Osteoarthritis: Comment on the Editorial by McAlindon

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