Articular Joint Lubricants during Osteoarthritis and Rheumatoid Arthritis Display Altered Levels and Molecular Species

Kosinska, Marta Krystyna; Ludwig, Taryn E.; Liebisch, Gerhard; Zhang, Ruiyan; Siebert, Hans‐Christian; Wilhelm, Jochen; Kaesser, U.; Dettmeyer, R.; Klein, Heiko; Ishaque, Bernd; Rickert, Markus; Schmitz, Gerd; Schmidt, Tannin A.; Steinmeyer, Jürgen

doi:10.1371/journal.pone.0125192

Cited by 160 publications

(171 citation statements)

References 45 publications

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“…Together, these findings imply that concentrations of various plasmalogen species were altered in OA, and plasmalogen derivates appear to be a predictor for cartilage degradation and inflammation in our obese mouse model. Our data are consistent with the results of a recent study showing that OA and rheumatoid arthritis patients had markedly increased plasmalogen levels in the synovial fluid as compared to healthy individuals, and the extent of increase in plasmalogen levels was disease-stage dependent22. Donovan et al .…”

Section: Discussionsupporting

confidence: 93%

Serum and synovial fluid lipidomic profiles predict obesity-associated osteoarthritis, synovitis, and wound repair

Kimmerling

Little

et al. 2017

Sci Rep

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High-fat diet-induced obesity is a major risk factor for osteoarthritis (OA) and diminished wound healing. The objective of this study was to determine the associations among serum and synovial fluid lipid levels with OA, synovitis, adipokine levels, and wound healing in a pre-clinical obese mouse model of OA. Male C57BL/6 J mice were fed either a low-fat (10% kcal) or one of three high-fat (HF, 60% kcal) diets rich in saturated fatty acids (SFAs), ω-6 or ω-3 polyunsaturated FAs (PUFAs). OA was induced by destabilization of the medial meniscus. Mice also received an ear punch for evaluating wound healing. Serum and synovial fluid were collected for lipidomic and adipokine analyses. We demonstrated that the serum levels of ω-3 PUFAs were negatively correlated with OA and wound size, but positively correlated with adiponectin levels. In contrast, most ω-6 PUFAs exhibited positive correlations with OA, impaired healing, and inflammatory adipokines. Interestingly, levels of pentadecylic acid (C15:0, an odd-chain SFA) and palmitoleic acid were inversely correlated with joint degradation. This study extends our understanding of the links of FAs with OA, synovitis and wound healing, and reports newly identified serum and synovial fluid FAs as predictive biomarkers of OA in obesity.

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Section: Discussionsupporting

confidence: 93%

Serum and synovial fluid lipidomic profiles predict obesity-associated osteoarthritis, synovitis, and wound repair

Kimmerling

Little

et al. 2017

Sci Rep

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“…Prior to translating lubricin supplementation therapy into humans, further investigation is warranted in clinically relevant large animal models such as the horse and in distinct types of joint injury, including both instability and intra-articular fracture models. The majority of evidence indicating that lubricin is depleted in joint injury has been derived from rodent models of knee instability 4–6 or in clinical cases of cruciate injury and late-stage knee OA in humans 5,7 , whereas data in human patients with intra-articular tibial plateau fracture 21 and in our equine osteochondral fragmentation model, lubricin is increased. Further mechanistic work is required to understand what role lubricin has following intra-articular fracture.…”

Section: Discussionmentioning

confidence: 99%

“…In human patients with anterior cruciate ligament (ACL) injury 4 and in rodent models of ACL injury 4–6 , synovial fluid lubricin concentrations are decreased in injured joints as compared to controls. Synovial fluid lubricin concentrations were also decreased in a population of human patients with late-stage OA and RA 7 . Mounting evidence suggests that lubricin supplementation, either through genetic overexpression 8 or recombinant lubricin supplementation 9–12 delays the progression of OA in rodent models.…”

Section: Introductionmentioning

confidence: 95%

Lubricin/proteoglycan 4 increases in both experimental and naturally occurring equine osteoarthritis

Reesink

Watts

Mohammed

et al. 2017

Osteoarthritis and Cartilage

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SUMMARY Objective The goals of this study were (1) to quantify proteoglycan 4 (PRG4) gene expression; (2) to assess lubricin immunostaining; and (3) to measure synovial fluid lubricin concentrations in clinical and experimental models of equine carpal osteoarthritis (OA). Design Lubricin synovial fluid concentrations and cartilage and synovial membrane PRG4 expression were analyzed in research horses undergoing experimental OA induction (n = 8) and in equine clinical patients with carpal OA (n = 58). Lubricin concentrations were measured using a custom sandwich enzyme-linked immunosorbent assay, and PRG4 expression was quantified using qRT-PCR. Lubricin immunostaining was assessed in synovial membrane and osteochondral sections in the experimental model. Results Lubricin concentrations increased in synovial fluid following induction of OA, peaking at 21 days post-operatively in OA joints vs sham-operated controls (331 ± 69 μg/mL vs 110 ± 19 μg/mL, P = 0.001). Lubricin concentrations also increased in horses with naturally occurring OA as compared to control joints (152 ± 32 μg/mL vs 68 ± 4 μg/mL, P = 0.003). Synovial membrane PRG4 expression increased nearly 2-fold in naturally occurring OA (P = 0.003), whereas cartilage PRG4 expression decreased 2.5-fold (P = 0.025). Lubricin immunostaining was more pronounced in synovial membrane from OA joints as compared to controls, with intense lubricin localization to sites of cartilage damage. Conclusions Although PRG4 gene expression decreases in OA cartilage, synovial membrane PRG4 expression, synovial fluid lubricin concentrations and lubricin immunostaining all increase in an equine OA model. Lubricin may be elevated to protect joints from post-traumatic OA.

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“…Recent studies indicate that decreased lubrication is also associated with the initiation and progression of OA in patients as well as in rodent models after anterior cruciate ligament injury [77][78][79][80]. Lubricin, a mucinous glycoprotein encoded by the proteoglycan 4 (Prg4) gene and a major component of synovial fluid, functions as both boundary lubrication and a chondro-protective agent in synovial joints [81,82].…”

Section: Hh Signaling In Degenerative Tmjsmentioning

confidence: 99%

The Roles of Indian Hedgehog Signaling in TMJ Formation

Bechtold

Kurio

Nah

et al. 2019

IJMS

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The temporomandibular joint (TMJ) is an intricate structure composed of the mandibular condyle, articular disc, and glenoid fossa in the temporal bone. Apical condylar cartilage is classified as a secondary cartilage, is fibrocartilaginous in nature, and is structurally distinct from growth plate and articular cartilage in long bones. Condylar cartilage is organized in distinct cellular layers that include a superficial layer that produces lubricants, a polymorphic/progenitor layer that contains stem/progenitor cells, and underlying layers of flattened and hypertrophic chondrocytes. Uniquely, progenitor cells reside near the articular surface, proliferate, undergo chondrogenesis, and mature into hypertrophic chondrocytes. During the past decades, there has been a growing interest in the molecular mechanisms by which the TMJ develops and acquires its unique structural and functional features. Indian hedgehog (Ihh), which regulates skeletal development including synovial joint formation, also plays pivotal roles in TMJ development and postnatal maintenance. This review provides a description of the many important recent advances in Hedgehog (Hh) signaling in TMJ biology. These include studies that used conventional approaches and those that analyzed the phenotype of tissue-specific mouse mutants lacking Ihh or associated molecules. The recent advances in understanding the molecular mechanism regulating TMJ development are impressive and these findings will have major implications for future translational medicine tools to repair and regenerate TMJ congenital anomalies and acquired diseases, such as degenerative damage in TMJ osteoarthritic conditions.

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Articular Joint Lubricants during Osteoarthritis and Rheumatoid Arthritis Display Altered Levels and Molecular Species

Cited by 160 publications

References 45 publications

Serum and synovial fluid lipidomic profiles predict obesity-associated osteoarthritis, synovitis, and wound repair

Serum and synovial fluid lipidomic profiles predict obesity-associated osteoarthritis, synovitis, and wound repair

Lubricin/proteoglycan 4 increases in both experimental and naturally occurring equine osteoarthritis

The Roles of Indian Hedgehog Signaling in TMJ Formation

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