A Dual Role of Upper Zone of Growth Plate and Cartilage Matrix–Associated Protein in Human and Mouse Osteoarthritic Cartilage: Inhibition of Aggrecanases and Promotion of Bone Turnover

Stöck, Michael; Menges, Stefanie; Eitzinger, Nicole; Geßlein, Maria; R, Botschner; Wormser, Laura; Distler, Alfiya; Schlötzer‐Schrehardt, Ursula; Dietel, Katharina; Distler, Jörg H W; Beyer, Christian; Gelse, Kolja; Engelke, Klaus; Koenders, Marije I.; Berg, W. van den; Mark, Klaus von der; Schett, Georg

doi:10.1002/art.40042

Cited by 26 publications

(43 citation statements)

References 43 publications

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“…In parallel, Seuffert et al suggested that UCMA can inhibit the aggrecanase activity of A Disintegrin and Metalloproteinase with Thrombospondin motifs 5 via binding and provides protection against cartilage degeneration . In addition, it was shown that UCMA deficiency resulted in reduced osteophyte formation and subchondral sclerosis . These results are in line with our findings and suggest that cartilage matrix can exert chondroprotective effects by augmenting UCMA synthesis against proteolytic deterioration in knee OA patients.…”

Section: Discussionsupporting

confidence: 92%

“…Recently, Stock et al demonstrated in vivo that UCMA was highly expressed in human and mouse cartilage tissues compared to control groups . These results are remarkable on the basis of underlying protective effects of UCMA in cartilage tissue during the course of OA.…”

Section: Discussionmentioning

confidence: 99%

“…UCMA, also known as GRP, is a member of vitamin K‐dependent family and it was reported in recent studies that UCMA plays significant roles in bone‐ and cartilage‐related processes of OA . However, to the best of our knowledge, the correlation between the severity of OA disease and UCMA levels in circulating blood and SF samples of knee OA patients has not yet been investigated.…”

Section: Discussionmentioning

confidence: 99%

“…These results are remarkable on the basis of underlying protective effects of UCMA in cartilage tissue during the course of OA. Furthermore, it was assessed that UCMA‐deficient mice had more propensity for OA‐induced cartilage damage and chondrocyte death . In parallel, Seuffert et al suggested that UCMA can inhibit the aggrecanase activity of A Disintegrin and Metalloproteinase with Thrombospondin motifs 5 via binding and provides protection against cartilage degeneration .…”

Section: Discussionmentioning

confidence: 99%

“…Under normal conditions, UCMA supports the integrity of the cartilage tissue and induces the subchondral bone cycle by inhibiting aggrecanase activity. Further, UCMA‐deficient mice have higher propensity for OA‐induced cartilage damage compared to wild type mice which indicated the potential chondroprotective effects of UCMA against OA . However, there are also some discrepancies about UCMA protein in the literature.…”

Section: Introductionmentioning

confidence: 99%

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Association of UCMA levels in serum and synovial fluid with severity of knee osteoarthritis

et al. 2019

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Aim Osteoarthritis (OA) is one of the most common joint diseases causing physical disability in the aged population. OA pathogenesis is not fully known and yet there are no effective therapeutic options against OA. Upper Zone of Growth Plate and Cartilage Matrix Associated (UCMA) is a member of vitamin K‐dependent protein family, and is involved in inflammation, cardiovascular diseases, cancer, and OA. In the present study, our aim was to detect serum and synovial fluid (SF) levels of UCMA and to analyze their correlation with radiographic findings and symptomatic severity in OA patients as well as the correlation between oxidative stress levels and SF UCMA levels. Methods Forty OA patients with cartilage degeneration and 20 patients with other knee joint disorders (non‐OA control) were included in the present study. We used the Kellgren‐Lawrence (KL) classification and Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores to assess radiographic grading and symptomatic severity of OA, respectively. UCMA levels were measured in SF and serum. And also oxidative stress markers were analyzed in SF. Results SF UCMA levels of OA patients were higher compared to those of the non‐OA control group and were positively correlated with radiographic finding and symptomatic severity of OA. However, there was no significant correlation between oxidative markers of SF and the KL grade, WOMAC scores, and SF UCMA levels in OA patients. Conclusion There is a close connection between UCMA SF levels and symptomatic and radiographic severities of knee OA. Therefore, UCMA can be a promising biomarker in the diagnosis and/or prognosis of OA disease.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association of UCMA levels in serum and synovial fluid with severity of knee osteoarthritis

et al. 2019

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Blocking PI3K/AKT signaling inhibits bone sclerosis in subchondral bone and attenuates post‐traumatic osteoarthritis

Lin

Shao

Zeng

et al. 2018

Journal Cellular Physiology

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PI3K/AKT signaling is essential in regulating pathophysiology of osteoarthritis (OA). However, its potential modulatory role in early OA progression has not been investigated yet. Here, a mouse destabilization OA model in the tibia was used to investigate roles of PI3K/AKT signaling in the early subchondral bone changes and OA pathological process. We revealed a significant increase in PI3K/AKT signaling activation which was associated with aberrant bone formation in tibial subchondral bone following destabilizing the medial meniscus (DMM), which was effectively prevented by treatment with PI3K/AKT signaling inhibitor LY294002. PI3K/AKT signaling inhibition attenuated articular cartilage degeneration. Serum and bone biochemical analyses revealed increased levels of MMP-13, which was found expressed mainly by osteoblastic cells in subchondral bone. However, this MMP-13 induction was attenuated by LY294002 treatment. Furthermore, PI3K/AKT signaling was found to enhance preosteoblast proliferation, differentiation, and expression of MMP-13 by activating NF-κB pathway. In conclusion, inhibition of PI3K/AKT/NF-κB axis was able to prevent aberrant bone formation and attenuate cartilage degeneration in OA mice.

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DNA methyltransferase genes polymorphisms are associated with primary knee osteoarthritis: a matched case–control study

et al. 2019

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A Dual Role of Upper Zone of Growth Plate and Cartilage Matrix–Associated Protein in Human and Mouse Osteoarthritic Cartilage: Inhibition of Aggrecanases and Promotion of Bone Turnover

Cited by 26 publications

References 43 publications

Association of UCMA levels in serum and synovial fluid with severity of knee osteoarthritis

Association of UCMA levels in serum and synovial fluid with severity of knee osteoarthritis

Blocking PI3K/AKT signaling inhibits bone sclerosis in subchondral bone and attenuates post‐traumatic osteoarthritis

DNA methyltransferase genes polymorphisms are associated with primary knee osteoarthritis: a matched case–control study

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