22 Publication(s) found
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Rheumatology, Osteoarthritis
7. Sep 2018

IL-37 diminishes proteoglycan loiss in human OA cartilage: donor-specific link between IL-37 and MMP-3.

OBJECTIVE:
A hallmark of osteoarthritis (OA) is degradation of articular cartilage proteoglycans. In isolated human OA chondrocytes, the anti-inflammatory cytokine Interleukin-37 (IL-37) lowers the expression of the proteolytic MMP and ADAMTS enzymes, which mediate this degradation. Therefore, we i…

Rheumatology, Osteoarthritis
29. Jul 2018

Tofacitinib and TPCA-1 Exert Chondroprotective Effects on Extracellular Matrix Turnover in Bovine Articular Cartilage Ex vivo.

OBJECTIVE:
Currently, there are no disease-modifying osteoarthritis drugs (DMOADs) approved for osteoarthritis. It is hypothesized that a subtype of OA may be driven by inflammation and may benefit from treatment with anti-inflammatory small molecule inhibitors adopted from treatments of rheumatoid…

Rheumatology, Rheumatoid Arthritis
8. May 2018

Type IV collagen metabolism is associated with disease activity, radiographic progression and response to tocilizumab in rheumatoid arthritis

OBJECTIVES:
The expanding spectrum of targeted therapies for rheumatoid arthritis (RA) implies a need for development of precision tools for disease assessment reflecting pathobiologic processes. Type IV collagen is an abundant protein of basement membranes, but is also present in the intercellular…

Rheumatology, Osteoarthritis
25. Apr 2018

Protein biomarkers associated with pain mechanisms in osteoarthritis

Osteoarthritis (OA) is the most common arthritic disease in the world, leading to debilitating pain and destruction of joint tissues. While pain is the hallmark symptom of osteoarthritis, clear associations between pain and disease processes involved in joint deterioration are lacking. OA pain is mu…

Rheumatology, Rheumatoid Arthritis
18. Apr 2018

Translational Biomarkers and Ex Vivo Models of Joint Tissues as a Tool for Drug Development in Rheumatoid Arthritis

OBJECTIVE:
Rheumatoid arthritis (RA) is a chronic, autoimmune and degenerative joint disease leading to disability, reduced life quality, and increased mortality. Although several synthetic and biological disease modifying anti-rheumatic drugs (DMARDs) are available, there is still a medical need f…

Bone, Extracellular Matrix Research, Osteoarthritis
10. Apr 2018

Osteoclasts degrade bone and cartilage knee joint compartments through different resorption processes

BACKGROUND:
Osteoclasts have been strongly implicated in osteoarthritic cartilage degradation, at least indirectly via bone resorption, and have been shown to degrade cartilage in vitro. The osteoclast resorption processes required to degrade subchondral bone and cartilage-the remodeling of which i…

Rheumatology, Rheumatoid Arthritis
31. Jan 2018

IL-6 receptor inhibition modulates type III collagen and C-reactive protein degradation in rheumatoid arthritis patients with an inadequate response to anti-tumour necrosis factor therapy: analysis of connective tissue turnover in the tocilizumab RADIATE.

OBJECTIVES:
The objective of this study was to examine the tissue degradation in response to anti-IL6 receptor treatment in rheumatoid arthritis (RA) patients which are anti-TNF-α inadequate responders.

METHODS:
RADIATE was a randomised, double-blinded, placebo-controlled, parallel-group, phase…

Rheumatology, Osteoarthritis
16. Oct 2017

Development and use of biochemical markers in osteoarthritis: current update

PURPOSE OF REVIEW:
There is an increasing demand for noninvasive and descriptive biochemical markers (biomarkers) in osteoarthritis; for enabling early drug development (including translational research), evaluating clinical trial at an early stage and for subtyping. Purpose of the review is to rev…

Rheumatology, Osteoarthritis
14. Oct 2017

Biochemical marker discovery, testing and evaluation for facilitating OA drug discovery and development

Osteoarthritis (OA) is the most common form of joint disease. This presents the OA research community and pharmaceutical companies developing disease-modifying OA drugs (DMOADs) with great opportunities. The different OA subtypes complicate the traditional approaches for developing new treatments. I…

Rheumatology, Osteoarthritis, Obesity
9. Sep 2017

A machine learning approach for the identification of new biomarkers for knee osteoarthritis development in overweight and obese women

OBJECTIVE:
Knee osteoarthritis (OA) is among the higher contributors to global disability. Despite its high prevalence, currently, there is no cure for this disease. Furthermore, the available diagnostic approaches have large precision errors and low sensitivity. Therefore, there is a need for new …

Extracellular Matrix Research, Osteoarthritis
22. Mar 2017

Biomarker of extracellular matrix remodelling C1M and proinflammatory cytokine IL-6 are related to synovitis and pain in endstage knee osteoarthritis patients

Little is known about local and systemic biomarkers in relation to synovitis and pain in end-stage osteoarthritis (OA) patients. We investigated the associations between the novel extracellular matrix biomarker, C1M, and local and systemic interleukin 6 (IL-6) with synovitis and pain. Serum C1M, pla…

Osteoporosis
3. Feb 2017

Forced expression of human M-CSF in CD34+ cells promotes monocyte differentiation in vitro and in vivo but blunts osteoclastogenesis in vitro

OBJECTIVES:
Here, we tested the hypothesis that human M-CSF (hM-CSF) overexpressed in cord blood (CB) CD34+ cells would induce differentiation and survival of monocytes and osteoclasts in vitro and in vivo.

METHODS:
Human M-CSF was overexpressed in cord blood CD34+ cells using a lentiviral vect…

Bone
19. Aug 2016

Regulation and Function of Lentiviral Vector-Mediated TCIRG1 Expression in Osteoclasts from Patients with Infantile Malignant Osteopetrosis: Implications for Gene Therapy

Infantile malignant osteopetrosis (IMO) is a rare, recessive disorder characterized by increased bone mass caused by dysfunctional osteoclasts. The disease is most often caused by mutations in the TCIRG1 gene encoding a subunit of the V-ATPase involved in the osteoclasts capacity to resorb bone. We …

Rheumatology, Osteoarthritis
25. Jan 2016

Osteoarthritis year in review 2015: soluble biomarkers and the BIPED criteria

OBJECTIVE:
To review and summarize biomarker data published from April 2014 to May 2015 to provide insight to the ongoing work in the field of osteoarthritis (OA). Furthermore, to summarize the BIPED criteria and set it in context of the medical needs of 2015.

METHODS:
PubMed was used as search…

Bone, Osteoporosis
10. May 2015

Novel targets for the prevention of osteoporosis - lessons learned from studies of metabolic bone disorders

Osteoporosis is a major health care problem, and whereas efficacious treatments for vertebral fracture reduction are available for osteoporosis patients, these therapies are still limited with respect to capacity for restoration of bone loss, as well as efficacy on non-vertebral fractures, such as h…

Bone
22. Jul 2014

A comparison of osteoclast-rich and osteoclast-poor osteopetrosis in adult mice sheds light on the role of the osteoclast in coupling bone resorption and bone formation

Osteopetrosis due to lack of acid secretion by osteoclasts is characterized by abolished bone resorption, increased osteoclast numbers, but normal or even increased bone formation. In contrast, osteoclast-poor osteopetrosis appears to have less osteoblasts and reduced bone formation, indicating that…

Bone
11. Dec 2013

Osteoclasts are not crucial for hematopoietic stem cell maintenance in adult mice

The osteoclast is vital for establishment of normal hematopoiesis in the developing animal. However, its role for maintenance of hematopoiesis in adulthood is more controversial. To shed more light on this process, we transplanted hematopoietic stem cells from two osteopetrotic mouse models, with la…

Bone
5. Nov 2013

Lentiviral gene transfer of TCIRG1 into peripheral blood CD34(+) cells restores osteoclast function in infantile malignant osteopetrosis

Infantile malignant osteopetrosis (IMO) is a rare, lethal, autosomal recessive disorder characterized by non-functional osteoclasts. More than 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. The aim of this study was to restore the resorpt…

Bone
29. Jul 2013

Lentiviral gene transfer of TCIRG1 into peripheral blood CD34+ cells restores osteoclast function in infantile malignant osteopetrosis

Infantile malignant osteopetrosis (IMO) is a rare, lethal, autosomal recessive disorder characterized by non-functional osteoclasts. More than 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. The aim of this study was to restore the resorpt…

Bone
16. Sep 2012

A specific subtype of osteoclasts secretes factors inducing nodule formation by osteoblasts

Osteoclasts are known to be important for the coupling process between bone resorption and formation. The aim of this study was to address when osteoclasts are anabolically active. Human monocytes were differentiated into mature osteoclasts by treatment with M-CSF and RANKL. Conditioned medium was c…

Bone, Osteoporosis
13. Mar 2012

Disruption of the V-ATPase functionality as a way to uncouple bone formation and resorption - a novel target for treatment of osteoporosis

The unique ability of the osteoclasts to resorb the calcified bone matrix is dependent on secretion of hydrochloric acid. This process is mediated by a vacuolar H+ ATPase (V-ATPase) and a chloride-proton antiporter. The structural subunit of the V-ATPase, a3, is highly specific for osteoclasts, and …

Bone
11. Jun 2011

Dissociation of bone resorption and bone formation in adult mice with a non-functional V-ATPase in osteoclasts leads to increased bone strength

Osteopetrosis caused by defective acid secretion by the osteoclast, is characterized by defective bone resorption, increased osteoclast numbers, while bone formation is normal or increased. In contrast the bones are of poor quality, despite this uncoupling of formation from resorption.To shed light …