The extent of degeneration of cruciate ligament is associated with chondrogenic differentiation in patients with osteoarthritis of the knee

Kumagai, Koshi; Sakai, Keiko; Kusayama, Yoshihiro; Akamatsu, Yasushi; Sakamaki, Kentaro; Morita, Satoshi; Sasaki, Takako; Saito, T.; Sakai, Takao

doi:10.1016/j.joca.2012.07.013

Cited by 26 publications

(39 citation statements)

References 41 publications

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“…Our findings of increased expression of genes of the WNT signaling pathway in the Achilles tendon-to-bone insertion of mstn −/− mice from neonatal to middle age support the hypothesis that myostatin deficiency contributes to ankle dysfunction. For instance, myostatin promotes tenocytes proliferation and differentiation while inhibiting chondrocyte differentiation in cell culture, indicating that myostatin may mitigate calcification and degeneration of juxta-articular ligaments (40–42). Myostatin also inhibits expression of BMP2 and IGF1, decreases osteoblast differentiation, and reduces mineral formation in bone marrow-derived mesenchymal stem cells (43, 44).…”

Section: Discussionmentioning

confidence: 99%

Joint dysfunction and functional decline in middle age myostatin null mice

Guo

Miller

Pencina

et al. 2016

Bone

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Since its discovery as a potent inhibitor for muscle development, myostatin has been actively pursued as a drug target for age- and disease-related muscle loss. However, potential adverse effects of long-term myostatin deficiency have not been thoroughly investigated. We report herein that male myostatin null mice (mstn−/−), in spite of their greater muscle mass compared to wild-type (wt) mice, displayed more significant functional decline from young (3–6 months) to middle age (12–15 months) than age-matched wt mice, measured as gripping strength and treadmill endurance. Mstn−/− mice displayed markedly restricted ankle mobility and degenerative changes of the ankle joints, including disorganization of bone, tendon and peri-articular connective tissue, as well as synovial thickening with inflammatory cell infiltration. Messenger RNA expression of several pro-osteogenic genes was higher in the Achilles tendon-bone insertion in mstn−/− mice than wt mice, even at the neonatal age. At middle age, higher plasma concentrations of growth factors characteristic of excessive bone remodeling were found in mstn−/− mice than wt controls. These data collectively indicate that myostatin may play an important role in maintaining ankle and wrist joint health, possibly through negative regulation of the pro-osteogenic WNT/BMP pathway.

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Section: Discussionmentioning

confidence: 99%

Joint dysfunction and functional decline in middle age myostatin null mice

Guo

Miller

Pencina

et al. 2016

Bone

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“…In this study, SOX9 staining was increased significantly in the cranial cruciate ligaments of the eTPA stifles compared to the control stifles. SOX9 is expressed in mesenchymal stem cells, pre-chondrocytes, and chondrocytes, and directs mesenchymal stem cells to undergo chondrogenic differentiation and activate transcription of chondrocyte-specific genes such as COLII (20). Bi and colleagues reported that SOX9-/-cells do not express chondrocytespecific markers, including COLII, and suggested SOX9 as the first transcription factor essential for chondrocyte differentiation and cartilage formation (23).…”

Section: Discussionmentioning

confidence: 99%

“…Bone attachment sites were excluded from the analysis. nate cellular long axis were defined as round ligamentocytes, and all other ligamentocytes were considered spindle ligamentocytes (20). The percentage of positive ligamentocytes was calculated as follows: (number of positive ligamentocytes/ total number of ligamentocytes) × 100.…”

Section: Postoperative Tpa and Mmptamentioning

confidence: 99%

Histological and immunohistological analysis of degenerative changes in the cranial cruciate ligament in a canine model of excessive tibial plateau angle

Ichinohe¹,

Kanno²,

Harada³

et al. 2015

Vet Comp Orthop Traumatol

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“…The relationship between ACL degeneration and OA has been examined in earlier studies (). Typically, degenerative changes in the ACL start with collagen fiber disorientation, followed by mucoid degeneration, inflammatory cell infiltration, and/or neovascularization.…”

Section: Discussionmentioning

confidence: 99%

“…It thus appears that ligament/tendon may contain a substantial proportion of progenitor cells. In OA, progenitor cells are activated, abnormally expressing SOX9 and differentiating to chondrocyte‐like cells (). Although these abnormal cells in degenerated ACLs are frequently positive for SOX9, other chondrogenic markers such as type II collagen or aggrecanase are not expressed by all of these cells.…”

Section: Discussionmentioning

confidence: 99%

Transcription Factor Mohawk and the Pathogenesis of Human Anterior Cruciate Ligament Degradation

Nakahara

Hasegawa

Otabe

et al. 2013

Arthritis & Rheumatism

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Objective To investigate the expression and function of Mohawk (MKX) in human adult anterior cruciate ligament (ACL) tissues and ligament cells from normal and osteoarthritis-affected knees. Methods Knee joints were obtained at autopsy within 24-48 hours postmortem from 13 normal donors (age 36.9±11.0 years), 16 OA donors (age 79.7±11.4 years) and 8 old donors without OA (age 76.9±12.9 years). All cartilage surfaces were graded macroscopically. MKX expression was analyzed by immunohistochemistry and quantitative PCR. ACL-derived cells were used to study regulation of MKX expression by IL-1β. MKX was knocked down by siRNA to analyze function of MKX in extracellular matrix (ECM) production and differentiation in ACL-derived cells. Results The expression of MKX was significantly decreased in ACL-derived cells from OA knees compared with normal knees. Consistent with this finding, immunohistochemistry showed that MKX positive cells were significantly reduced in ACL tissues from OA donors in particular in cells located in disorientated fibers. In ACL-derived cells, IL-1β strongly suppressed MKX gene expression and reduced ligament ECM genes, COL1A1 and TNXB. On the other hand, SOX9, chondrocyte master transcription factor, was up regulated by IL-1β treatment. Importantly, knock down of MKX expression by siRNA upregulated SOX9 expression in ACL-derived cells, whereas the expression of COL1A1 and TNXB were decreased. Conclusion Reduced expression of MKX is a feature of degenerated ACL in OA-affected joints and this may be in part mediated by IL-1β. MKX appears necessary to maintain the tissue specific cellular differentiation status and ECM production in adult human tendons and ligaments.

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The extent of degeneration of cruciate ligament is associated with chondrogenic differentiation in patients with osteoarthritis of the knee

Cited by 26 publications

References 41 publications

Joint dysfunction and functional decline in middle age myostatin null mice

Joint dysfunction and functional decline in middle age myostatin null mice

Histological and immunohistological analysis of degenerative changes in the cranial cruciate ligament in a canine model of excessive tibial plateau angle

Transcription Factor Mohawk and the Pathogenesis of Human Anterior Cruciate Ligament Degradation

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