Health Relevance

MOLECULAR AND CELLULAR APPROACHES TO DETECT AND TREAT OSTEOARTHRITIS

Osteoarthritis is a major obstacle to work productivity and quality of life for many Canadians, affecting over 10% of the general population, with the elderly increasingly afflicted (~50% of Canadians over 60 years old). In osteoarthritis, cartilage breaks down at the interacting surfaces of bones (i.e., joints), and its absence causes pain and immobility. The research program on osteoarthritis in the Eames lab has many complementary components. To help prevent painful symptoms of osteoarthritis, our research aims to diagnose it at earlier stages, prior to the onset of severe tissue loss. Using novel genetic and imaging techniques, we hope to to facilitate early diagnosis by revealing the molecular and genetic basis for osteoarthritis. Other projects in the Eames lab utilize tissue engineering to provide therapeutic treatment for osteoarthritic tissues that are diagnosed in the late stages of disease progression.

I. Proteoglycan loss alone causes a broad spectrum of OA pathology

By revealing the molecular genetic basis of osteoarthritis, we can design new genetic and molecular diagnostics for early detection. At the cellular and molecular level, osteoarthritis involves three main defects: 1) degradation of sugar-coated proteins (proteoglycans) in joint cartilage, 2) changes to gene expression in the cells (chondrocytes) that maintain joint cartilage, and 3) extra bone formation in adjacent regions. The Eames lab uses unique genetic and imaging tools to test the hypothesis that cartilage proteoglycan degradation actually causes changes to chondrocyte gene expression and adjacent bone formation.

For over 15 years, our vertebrate cousin, the zebrafish, has been a widely-accepted research model of human development and disease. The Eames lab has zebrafish with unique mutations in cartilage proteoglycan production. These fish showed that loss of proteoglycans itself causes changes to chondrocyte gene expression and adjacent bone formation. This novel experimental system provides a fresh, unexplored avenue for understanding and eventually treating osteoarthritis. Specifically, we study the molecular mechanism by which proteoglycans change chondrocyte gene expression, hypothesizing that proteoglycans in the cartilage modulate the biological activity of secreted growth factors, which in turn alter chondrocyte gene expression and adjacent bone formation. To test this hypothesis, we use many powerful experimental tools available in zebrafish (e.g., mutants, transgenics, and embryonic injections) to manipulate the proteoglycan levels in cartilage matrix and/or growth factor activity. We measure the effects of proteoglycans and growth factor activity on chondrocyte gene expression using a variety of histological and molecular assays.

II. Chemical-specific imaging as a readout of proteoglycan function

In a complementary line of research to develop early diagnostics for osteoarthritis, the Eames lab uses novel imaging techniques being developed at the University of Saskatchewan to assay the importance of specific chemical elements in proteoglycan function. Using the Canadian Light Source synchrotron on campus here, we produce images with high spatial resolution that reflect the exact molecular composition of cartilage tissue samples. Our unique imaging methods reveal spatial patterns of specific chemicals in normal, intact cartilage matrix and also the variety of changes that may occur in proteoglycan-deficient cartilage matrix of zebrafish mutants. By associating specific chemical elements with the structural integrity of cartilage, these experiments may lead to novel imaging methods for diagnosing osteoarthritis in the clinic.

III. Tissue engineering of articular cartilage

Since most cases of osteoarthritis in the clinics are diagnosed after severe cartilage loss has occurred in skeletal joints of patients, a promising therapy of the future involves tissue engineering of cartilage. The use of biodegradable scaffolds embedded with cells shows promise for articular cartilage repair. The Tissue Engineering Research Group, led by Dr. Daniel Chen, believe significant advances in cartilage replacement therapy for osteoarthritis patients can be made by engineering scaffolds with carefully controlled microstructure and arrangements of cells, tailored to mimic the organization of native articular cartilage. To this end, we are developing novel methods to advance the theoretical and practical basis of producing biodegradable scaffolds for cartilage replacement in osteoarthritis patients. We are testing these advanced scaffolds for their ability to promote cartilage regeneration in culture dishes, then in small animal models, such as the miniature pig.

Grants

(Those NOT awarded through competitive peer-review are italicized) Total amount: $4,926,000

Year

Amount

Agency

Award

Title

2022-2023

150,000

Natural Sciences and Engineering Research Council (NSERC)

Research Tools and Instruments (RTI) (1 of 6 Co-Applicants)

High Efficiency X-ray Macroscope for Biomedical Imaging at the Canadian Light Source Synchrotron

2020-2021

150,000

Natural Sciences and Engineering Research Council (NSERC)

Research Tools and Instruments (RTI) (1 of 8 Co-Applicants)

A cutting-edge mechanical simulation bioreactor for tissue engineering

2019-2024


180,000

Natural Sciences and Engineering Research Council (NSERC)

Discovery Grant (Sole Investigator)

Evolution of skeletal cell transcriptomes

2018-2019

150,000

Natural Sciences and Engineering Research Council (NSERC)

Research Tools and Instruments (RTI) (1 of 5 Co-Applicants)

A cutting-edge printer for bio-fabricating tissue scaffolds

2018-2019

8,000

LabEX CeMEB (France)

Invited Scientist Grant (Sole Investigator)

Collaboration with Melanie Debiais-Thibaud (Univ. Montpellier)

2018-2019


34,000

UofS CoM OVDR

Research Cluster Funding (Principal of 13 Co-Applicants)

Imaging and Development cluster

2018-2019

5,000

UofS Office Vice President Research

Sabbatical Leave Grant (Sole Investigator)

Travel for sabbatical collaborations

2018-2019

5,000

UofS Office Vice President Research

Global Ambassador (Outgoing)—(Sole Investigator)

Travel for sabbatical collaborations

2018-2020

100,000

University of Saskatchewan College of Medicine

CoMBRIDGE operating grant (Principal of 4 Co-Applicants)

Establishing a pig model for cartilage tissue engineering

2018-2019

50,000

Saskatchewan Health Research Foundation (SHRF)

Collaborative Innovation Development Grant (1 of 6 Co-Applicants)

Synchrotron imaging-based non-invasive studies on 3D printed scaffolds for bone repair

2018-2019

41,000

Natural Sciences and Engineering Research Council (NSERC)

Discovery Grant Extension (Sole Investigator)

Evolution of skeletal cell transcriptomes

2017-2018

102,000

Canada Council for the Arts (CCA)

Explore and Create (New Media Arts)—(1 of 2 Co-Applicants)

All forms at all times

2016-2024

753,035

Canadian Institutes of Health Research (CIHR)

Operating Grant (Sole Investigator)

Mechanisms and effects of proteoglycan-dependent signalling in skeletal tissues

2016

50,200

Canada Council for the Arts (CCA)

New Media and Audio Artists: Research and Production Grant—(1 of 2 Co-Applicants)

Morphogenesis: Collaborative art-science laboratory residency and evolutionary science project culminating in immersive digital art exhibition

2015-2016

100,000

Canadian Institutes of Health Research (CIHR)

Operating Grant; Bridge funding: New Investigator, Musculoskeletal, Skin, and Oral Health—(Principal of 2 Co-Applicants)

Zonal articular cartilage tissue engineering

2015

1,259,321

Canada Foundation for Innovation (CFI)

John R. Evans Leaders Fund—(1 of 2 Co-Applicants)

High-throughput molecular imaging platform

2014

61,736

Natural Sciences and Engineering Research Council (NSERC)

Research Tools and Instruments (RTI)—(1 of 3 Co-Applicants)

X-ray tube replacement for micro-CT imaging of musculoskeletal development and adaptation

2014-2019

300,000

Canadian Institutes of Health Research (CIHR)—RPP SK

New Investigator Salary Award (Sole Investigator)

Deciphering the functional role of proteoglycans in the etiology of osteoarthritis

2013-2018

205,000

Natural Sciences and Engineering Research Council (NSERC)

Discovery Grant (Sole Investigator)

Evolution of skeletal cell transcriptomes

2013-2014

25,000

Royal University Hospital Foundation (RUHF)

RUHF Research Grant (Principal of 5 Co-applicants)

Improved imaging for osteoarthritis

2013-2016

750,000

Saskatchewan Health Research Foundation (SHRF)

Health Research Group (Phase 3)—(1 of 10 Co-Applicants)

Tissue Engineering Research Group

2012-2015

120,000

Saskatchewan Health Research Foundation (SHRF)

Establishment Grant (Sole Investigator)

Temporal regulation of skeletal cell differentiation by proteoglycan-dependent growth factor signalling

2012-2015

110,000

University of Saskatchewan (Provost, College of Medicine, Dept. of Anatomy & Cell Biology)

Start-up

Temporal regulation of skeletal cell differentiation by proteoglycan-dependent growth factor signalling

Dept. Anatomy, Physiology, and Pharmacology,
107 Wiggins Rd,
Saskatoon, SK, Canada, S7N 5E5

 

Office: 2D01.3 HSC, (306)966-6534
Lab: B314 HSC, (306)966-4087