Karen B. King Assistant Professor Department of Orthopaedics, Division of Bioengineering Director, Orthopaedic Molecular Biology Laboratory Ph.D., Biochemistry, Rush University, Chicago, IL, 1996 Office: UC D - Anschutz Medical Campus Academic Offices 1, Room 4511 Phone: 303-724-1596 Laboratory: RC1-South, Rm P18-2401 UCHSC, Box 8120 12801 East 17th Ave Aurora, CO 80045 Phone: 303-724-1573 or 4-0899 Email: Karen.King@ucdenver.edu

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Departmental Affiliations Department of Orthopaedics, Division of Bioengineering Orthopaedic Molecular Biology Laboratory

Research

Our primary research interest is to elucidate the cause and progression of osteoarthritis and other degenerative joint diseases, specifically to define the relationship between mechanical joint loading and tissue metabolic changes that cause and/or exacerbate cartilage and bone pathology. Our approach is multi-disciplinary, involving molecular biology, biochemistry, mechanobiology, cell biology, biomarker analysis, imaging, biomechanics, and tissue engineering.

We use an in vivo animal model to create cyclical joint loading that simulates repetitive hand motions found in the workplace (e.g., dentistry/dental hygiene, factory/manufacturing). In this model loading force, frequency, and rate are precisely controlled which allows us to determine the relative importance of these individual biomechanical factors, for example, to elucidate which loading levels are injurious and to subsequently define cause and effect between hand tasks and injury. This project takes advantage of both in vivo and in vitro approaches to determine how cells and tissues and tissue engineered constructs respond to mechanical forces. Data from this project will contribute to:

• preventing occupational joint disorders by defining which loading patterns are harmful
• identifying the metabolic mechanisms of mechanical joint loading
• creating mechanically functional engineered joint tissues

A new research project examines the co-morbidity of diabetes in orthopaedics. The goal of this project is to determine how the metabolic abnormalities of chondrocytes and osteocytes from patients with insulin resistance, impaired glucose tolerance, and diabetes impair post-operative healing of total joint replacement. This project uses biochemistry and cell culture techniques to identify metabolic abnormalities that lead to detrimental changes in tissue structure-relevant molecules such as collagen, proteoglycans, matrix metalloproteinases. Data from this project will contribute to:

• understanding the effects of diabetes on skeletal tissues
• identifying risk factors for poor surgical outcome
• creating strategies for improving future surgical outcomes

Selected Publications

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.

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.

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.

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.

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.

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.

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, 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.

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.

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.

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.

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.

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.

Latest Publications in PubMed