The relationship between fibrogenic TGFβ1 signaling in the joint and cartilage degradation in post-injury osteoarthritis

Plaas, Anna; Velasco, Jennifer; Gorski, Daniel J.; Li, J.; Cole, Ada A.; Christopherson, Kent W.; Sandy, John D.

doi:10.1016/j.joca.2011.05.003

Cited by 53 publications

(53 citation statements)

References 129 publications

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“…Before drawing conclusions regarding the role of these proteases in the development of posttraumatic OA, these patients will need to be followed over time to evaluate if these MMPs and aggrecan degradation are more strongly correlated with the ultimate development of posttraumatic OA. Prior studies have suggested various cell-signaling mechanisms that may play a role in the development of posttraumatic OA including transforming growth factor-b, endothelin-1, interleukin-1b, and NF-jB [12,15,22,33,37,38]. Our current study should draw attention to the postinjury presence of MMPs and aggrecan degradation as potentially playing a role in progression to OA as well.…”

Section: Discussionmentioning

confidence: 83%

Intraarticular Matrix Metalloproteinases and Aggrecan Degradation Are Elevated After Articular Fracture

Haller

Swearingen

Partridge

et al. 2015

Clin Orthop Relat Res

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Background Posttraumatic osteoarthritis (OA) is a variant of OA that can develop after articular injury. Although the mechanism(s) of posttraumatic OA are uncertain, the presence and impact of postinjury proteolytic enzymes on articular cartilage remain unknown. To our knowledge, there are no studies that evaluate the presence of matrix metalloproteinases (MMPs) or aggrecan degradation after articular fracture.Questions/purposes (1) Are MMP concentrations and aggrecan degradation elevated after intraarticular fracture? (2) Are MMP concentrations and aggrecan degradation greater in high-energy injuries compared with low-energy injuries? (3) Do the concentrations of these biomarkers remain elevated at a secondary aspiration? Methods Between December 2011 and June 2013, we prospectively enrolled patients older than 18 years of age with acute tibial plateau fracture. Exclusion criteria included age older than 60 years, preexisting knee OA, injury greater than 24 hours before evaluation, contralateral knee injury, history of autoimmune disease, open fracture, and non-English-speaking patients. During the enrollment period, we enrolled 45 of the 91 (49%) tibial plateau fractures treated at our facility. Knee synovial fluid aspirations were obtained from both the injured and uninjured knees; two patients received aspirations in the emergency department and the remaining patients received aspirations in the operating room. Twenty patients who underwent spanning external fixator followed by definitive fixation were aspirated during both surgical procedures. MMP-1, -2, -3, -7, -9, -10, -12, and -13 concentrations were quantified using multiplex assays. Aggrecan degradation was quantified using sandwich enzyme-linked immunosorbent assay. Results There were higher concentrations of MMP-1 (3.89 ng/mL [95% confidence interval {CI}, 2.37-6.37] versus 0.37 ng/mL [95% CI, 0.23-0.61], p \ 0.001), MMP-3The institution of one or more of the authors (JMH, TFH) has received peer-reviewed research grant funding from the Orthopedic Trauma Association, LS Peery Foundation, and AO North America for this project. One of the authors certifies that he (TFH), or a member of his immediate family, has signed an agreement with DePuy Synthes (Warsaw, IN, USA) for consulting activities not related to the current study, and has not received payments or benefits, during the study period. One or more of the authors (CAS, KT) are employed at Eli Lilly (Indianapolis, IN, USA). All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research1 editors and board members are on file with the publication and can be viewed on request. Clinical Orthopaedics and Related Research1 neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDAapproval status, of any drug or device prior to clinical use. Each author certifies that his or her institution approved or waived approval for the reporting of this investigation and that all inves...

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Section: Discussionmentioning

confidence: 83%

Intraarticular Matrix Metalloproteinases and Aggrecan Degradation Are Elevated After Articular Fracture

Haller

Swearingen

Partridge

et al. 2015

Clin Orthop Relat Res

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“…This may reduce the need for application of growth factors like FGF2, TGFb 1 and PDGFb, which are expensive and have been shown to be associated with degenerative processes in osteoarthritis. 30,33,34,40 To gain an understanding of the mechanistic signaling pathways governing the observed effects of HIFBS treatment to chondrocytes, MAP kinase activity was assessed. It has been established that ERK1/2 activity increases during passage-induced dedifferentiation, 41 and moreover, changes in MAPK signals in general have been correlated with negative effects to chondrocyte phenotype.…”

Section: Discussionmentioning

confidence: 99%

Protection of Bovine Chondrocyte Phenotype by Heat Inactivation of Allogeneic Serum in Monolayer Expansion Cultures

Matmati

Rosenzweig

et al. 2013

Ann Biomed Eng

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Cartilage defects can be addressed with replacement strategies such as autologous chondrocyte implantation (ACI). Expansion of autologous chondrocytes in vitro is an essential step to obtain the necessary cell numbers required for ACI. A major problem with this approach is dedifferentiation of chondrocytes during expansion, resulting in cells with fibroblast-like features. These cells generate cartilage tissue with fibrotic instead of hyaline characteristics. The use of serum is a common feature in most expansion protocols and a potential factor contributing to the dedifferentiation process. The aim of this study was to assess if heat inactivation of serum used in the expansion medium might be a valid approach to generate cells with an improved phenotype and in relevant numbers. We used bovine chondrocyte expansion cultures incubated with heat inactivated allogeneic serum (HIFBS) as a model system. We here show that heat inactivation protects the differentiated phenotype of chondrocytes compared to cultures with regular serum. This is not only true for primary cultures but holds up after two passages. Moreover, using relatively low cell seeding densities, clinically relevant cell numbers can already be reached after the first passage in cultures with HIFBS. In short we here introduce a simple way to improve cell quality while generating relevant amounts of cells during monolayer expansion of bovine chondrocytes in a relative short time period. Our results could have wider implications when translated to the expansion of human chondrocytes.

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“…Stem cell function is associated with the recovery of articular cartilage injury and with the pathomechanism of post-traumatic osteoarthritis [59,60]. In response to injury, MSC within articular cartilage differentiate to produce fibroblastic cells instead of chondrogenic cells.…”

Section: Stem Cells In Chondral Healingmentioning

confidence: 99%

Trauma and Stem Cells: Biology and Potential Therapeutic Implications

Thurairajah

Broadhead

Balogh

2017

IJMS

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Trauma may cause irreversible tissue damage and loss of function despite current best practice. Healing is dependent both on the nature of the injury and the intrinsic biological capacity of those tissues for healing. Preclinical research has highlighted stem cell therapy as a potential avenue for improving outcomes for injuries with poor healing capacity. Additionally, trauma activates the immune system and alters stem cell behaviour. This paper reviews the current literature on stem cells and its relevance to trauma care. Emphasis is placed on understanding how stem cells respond to trauma and pertinent mechanisms that can be utilised to promote tissue healing. Research involving notable difficulties in trauma care such as fracture non-union, cartilage damage and trauma induced inflammation is discussed further.

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The relationship between fibrogenic TGFβ1 signaling in the joint and cartilage degradation in post-injury osteoarthritis

Cited by 53 publications

References 129 publications

Intraarticular Matrix Metalloproteinases and Aggrecan Degradation Are Elevated After Articular Fracture

Intraarticular Matrix Metalloproteinases and Aggrecan Degradation Are Elevated After Articular Fracture

Protection of Bovine Chondrocyte Phenotype by Heat Inactivation of Allogeneic Serum in Monolayer Expansion Cultures

Trauma and Stem Cells: Biology and Potential Therapeutic Implications

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