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Karen B. King, Ph.D. - Director

Research Program

The long-term goals of the research in this laboratory are to elucidate the causes of the initiation and progression of osteoarthritis and other degenerative joint diseases and to create and improve treatment and prevention strategies. The approach is multi-disciplinary using techniques from molecular biology, biochemistry, mechanobiology, cell biology, biomarker analysis, imaging, biomechanics, and tissue engineering.

We study in vivo cyclical joint loading using a novel animal model of repetitive finger joint flexion. Force and frequency are precisely controlled, and outcome measures include histological analysis of cartilage and bone morphology, biochemical and spectral characterization of extracellular matrix components, and analysis of mechanical properties. Using this model, we identified a significant increase in proteoglycan in the cartilage deep zone (measured using Fourier-transform infrared microspectroscopy). We also mesasured an increase in the number of chondrocytes producing osteopontin, a protein involved in mineralization.

 

The laboratory collaborates with the Musculoskeletal Disorders Lab in identifying inflammatory agents in soft tissue exposed to cyclic and static loading.

 

Facilities & Equipment

Facilities
1,600 square feet of laboratory space
300 square foot cold room
Access to electronic and mechanical shops

Equipment
Animal anesthesia equipment

Electrical muscle stimulator, A/D board, amplifier, data acquisition workstation, load cells

HPLC workstation, software, auto-sampler, dual pumps, UV detector, fluorescence detector

Vacuum centrifuge concentrator

Multi-well plate reader with workstation and data analysis software, multi-well plate washer, multi-well plate shaker

Histology tissue processor, paraffin embedder, rotary microtome, slide dryer

Light and fluorescence microscope, digital camera, digital imaging and image analysis software

Electrophoresis units, mini-electrophoresis units, electrical transfer units, semi-dry electrical transfer unit, power supply units

Tissue dimembranator (tissue mill)

Hybridization oven, UV cross-linker DNA/RNA horizontal gel electrophoresis units

Cell culture incubators, bio-safety laminar flow hood

Refrigerated centrifuge, micro-centrifuges

Autoclave

Electrical balances, pH meters

-80 freezers, -20 freezer, refrigerator
Computer workstations

 

Research Projects
Current research projects include:

  • Cyclical finger loading: the effect of force and frequency on cyclical articular joint loading in vivo
  • Arthroplasty outcomes in diabetics: bone and cartilage metabolism

 

Graduate Students
Ph.D. students are accepted into this lab through the University of Colorado Denver’s Cell Biology, Stem Cells, and Development Graduate Program. Additional information on the graduate program is available at: http://www.uchsc.edu/cdb/     Applications are available at: http://www.uchsc.edu/gs/gs/

 

Research Residents

Trevor Oren, MD, (2007-present)

Arthroplasty outcomes in diabetics: bone metabolism and clinical biomarkers.

 

Medical Students

Keely Chevalier          (2008-        )

Imran Choudhry         (2007-2008) Jointly supervised with Dr. M. Solomonow.

Julian Ku                    (2008-        ) Jointly supervised with Dr. M. Solomonow.

 

Fellows

Navid Ziran                (2007-2008) Jointly supervised with Dr. D. Hak.

The effect of age on in vivo bone formation by rat marrow stem cells.

 

Research Student Interns

HoanVu Ngyuen         (summer 2008) Rangeview High School

Ananth Sridar             (summer 2007) Stanford University

 

Publications

Publications

KB King, S Chubinskaya, DL Reid, LH Madsen, and J Mollenhauer. Absence of cell-surface annexin V is accompanied by defective collagen matrix binding in the Swarm rat chondrosarcoma. Journal of Cellular Biochemistry. 65:131-144, 1997.

 

J Mollenhauer, MT Mok, KB King, M Gupta, S Chubinskaya, H Koepp, and AA Cole. Expression of anchorin CII (cartilage annexin V) in human young, normal adult, and osteoarthritic cartilage. Journal of Histochemistry and Cytochemistry. 47:209-220, 1999.

 

L Jennings, L Wu, KB King, H Hämmerle, G Cs-Szabo, and J Mollenhauer. The effects of collagen fragments on the extracellular matrix metabolism of bovine and human chondrocytes. Connective Tissue Research. 42:71-86, 2001.

 

D Heinegård, K King, M Mörgelin, K Rosenberg, and C Wiberg. Matrix molecules with roles in cartilage assembly. In: Molecular Biology in Orthopaedics. RN Rosier and CH Evans, editors. American Academy of Orthopaedic Surgeons, Rosemont, IL, pp. 315-325, 2003.

 

KB King and JH Kimura. The establishment and characterization of an immortal cell line with a stable chondrocytic phenotype. Journal of Cellular Biochemistry. 89:992-1004, 2003.

 

KB King, CT Lindsey, MD Ries, LS Steinbach, and S Majumdar. A study of the relationship between molecular biomarkers of joint degeneration and the magnetic resonance-measured characteristics of cartilage in 16 symptomatic knees. Magnetic Resonance Imaging. 22:1117-1123, 2004.

 

A Mündermann, CO Derby, TP Andriacchi, and KB King. Serum concentration of cartilage oligomeric matrix protein (COMP) is sensitive to physiological cyclic loading in healthy adults. Osteoarthritis and Cartilage. 13:34-38, 2005.

 

LH Nakama, KB King, SO Abrahamsson, and D Rempel. Evidence of microtears due to cyclical loading in an in vivo tendinopathy model. Journal of Orthopaedic Research. 23:1199-1205, 2005.

 

KB King, C Opel, and D Rempel. Cyclical articular joint loading leads to cartilage thinning and osteopontin production in a novel in vivo rabbit model of repetitive finger flexion with loading. Osteoarthritis and Cartilage. 13:971-978, 2005.

 

LH Nakama, KB King, SO Abrahamsson, and D Rempel. VEGF, VEGFR-1, and CTGF cell densities in tendon are increased with cyclical loading: An in vivo tendinopathy model. Journal of Orthopaedic Research. 24:1-9, 2006.

 

C Li, LA Pruitt, and KB King. Nanoindentation differentiates tissue-scale functional properties of native articular cartilage. Journal of Biomaterials Research. 17A:729-738, 2006.

 

E Saadat, H Lan, S Majumdar, DM Rempel and KB King. Long-term cyclical in vivo loading increases cartilage proteoglycan content in a spatially specific manner: an infrared microspectroscopic imaging and polarized light microscopy study. Arthritis Research and Therapy. 8:R147, 2006.

 

LH Nakama, KB King, S Abrahamsson, DM Rempel. Effect of Repetition Rate on the Formation of Microtears in Tendon in an In Vivo Cyclical Loading Model. Journal of Orthopaedic Research. 25:1176-1184. 2007.

KR Asundi, KB King, and DM Rempel. Evaluation of gene expression through qRT-PCR in cyclically loaded tendons: an in vivo animal model. European Journal of Applied Physiology. 102:265-270, 2008.

 

C Li, KB King, and LA Pruitt. Zone-specific changes in micromechanical, biochemical, and structural properties in articular cartilage from a rabbit joint flexion model. Materials Research Society Symposium Proceedings. 1097E:1-6, 2008.

 

 

Funding

R01 OH007786

P30  DK57516


 
 
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