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Laboratory of Susan Chubinskaya, PhD

The research of Susan Chubinskaya, PhD, focuses on the molecular and mechanical mechanisms of human cartilage degeneration and osteoarthritis.

Our work

Our early publications addressed the mechanisms of cartilage degeneration in human cartilage. We have identified and characterized a third matrix metalloproteinase in cartilage. Prior to our work MMP-8 was found only in neutrophils and was not known in human cartilage. We identified the patterns of its gene and protein expression in normal human cartilage and in cartilage aging and OA in contrast to other, well-known at that time collagenase, MMP-1. We also identified the mechanisms of MMP-8 regulation by catabolic mediators. This body of work has added to our understanding of the spectrum of MMPs that are responsible for collagen breakdown.

We also have a unique collaboration with the Organ Bank of Illinois that provides our group with access to human cartilage specimens that are obtained from knees and ankles of asymptomatic donors. To date, we have collected and characterized about 15,000 joints. Often, we receive four intact joints from a single donor. We have effectively characterized the morphological appearance of articular cartilage from all types of human synovial joints and at all stages of cartilage degeneration using a modified Mankin scoring system. We have identified and characterized biochemical differences between cartilage from the knee and ankle joints, leading to a better understanding of why knee osteoarthritis is more prevalent than ankle osteoarthritis. This access to and investigation of human fresh donor tissues has changed the osteoarthritis research landscape. Supported by both federal and non-federal funding, this program has resulted in multiple national and international collaborations.

Another one of our key contributions to the musculoskeletal field is our work in Bone Morphogenic Protein-7/Osteogenic Protein-1. We were the first group to identify and characterize OP-1 gene and protein in normal, aging, and diseased human cartilage. We have also developed a new methodology to study OP-1: we use ELISA to measure OP-1 levels in human tissues, and then use R-Smad linker region antibodies to investigate the underlying signaling mechanisms of action. Further, we have shown OP-1’s vital role in cartilage homeostasis and cartilage anabolism/catabolism. This was pioneering work in the field of growth factors, and to date, we remain the world experts in the field of growth factors (especially BMPs) in human cartilage. This work has resulted in multiple collaborative research projects, and has been continuously funded by both NIH and private industry.

More recently, through collaboration with Markus Wimmer, PhD, director of the gait laboratory at Rush, we have also laid the groundwork for understanding the early cellular responses in post-traumatic OA. Using a model of acute trauma in human ankle cartilage, we have not only identified key cellular responses in PTOA, we have also evaluated the efficacy of targeted biologic PTOA interventions. Further, we have studied the response of human cartilage to different material and mechanical environments in comparison with our computational models of cartilage-cartilage articulation.

Selected publications

Mechanisms of MMP-8 regulation by catabolic mediators in Osteoarthritis

  • Cole AA, Chubinskaya S, Schumacher B, Huch K, Cs-Szabo G, Yao J, Mikecz K, Hasty KA, and Kuettner KE. Chondrocyte MMP-8: Human articular chondrocytes express neutrophil collagenase. Journal of Biological Chemistry. 1996. 271(18):11023-6.
  • Chubinskaya S, Huch K, Mikecz K, Cs-Szabo G, Hasty KA, Kuettner KE, and Cole AA. Chondrocyte matrix metalloproteinase-8: Up-regulation of neutrophil collagenase by interleukin-1ß in human cartilage from knee and ankle joints. Journal of Laboratory Investigation. 1996. 74(1):232-40.
  • Shlopov BV, Lie WR, Mainardi CL, Chubinskaya S, Cole AA, and Hasty KA. Osteoarthritic lesions: involvement of three different collagenases. Arthritis and Rheumatism. 1997. 40(11):2065-74.
  • BÜttner FH, Chubinskaya S, Margerie D, Huch K, Flechtenmacher J, Cole AA, Kuettner KE, and Bartnik E. Membrane type matrix metalloproteinase (MT-MMP) is expressed in human articular cartilage. Arthritis and Rheumatism. 1997. 40(4):704-9.

Mechanisms of Cartilage Degeneration in Human Osteoarthritis

  • Chubinskaya S, Huch K, Schulze M, Otten L, Aydelotte MB, and Cole AA. Human articular chondrocytes cultured in alginate beads maintain their gene expression. Cells and Materials. 1998. 8:151-60.
  • Mollenhauer J, Mok MT, King KB, Gupta M, Chubinskaya S, Koepp H, and Cole AA. Expression of anchorin CII (cartilage annexin V) in human young, normal adult and osteoarthritic cartilage. Journal of Histochemical Cytochemistry. 1999. 47(2):209-20.
  • Chubinskaya S, Kuettner KE, and Cole AA. Expression of matrix metalloproteinases in human normal and damaged articular cartilage from knee and ankle joints. Journal of Laboratory Investigation. 1999. 79(12):1669-77.
  • Chubinskaya S, Huch K, Schulze M, Otten L, Aydellotte MB, and Cole AA. Gene expression by human articular chondrocytes cultured in alginate beads. Journal of Histochemical Cytochemistry. 2001. 49(10): 1211-1219.
  • Chubinskaya S, Jacquet R, Isogai N, Asamura S, and Landis WJ. Characterization of the Cellular Origin of a Tissue-engineered Human Phalanx Model by in situ Hybridization. Tissue Engineering. 2004. 10(7): 1204-1213.

BMP-7 in Cartilage Homeostasis

  • Chubinskaya S, Merrihew C, Cs-Szabo G, Mollenhauer J, McCartney J, Rueger DL, and Kuettner KE. Human articular chondrocytes express osteogenic protein-1. 2000. Journal of Histochemical Cytochemistry. 48 (2):239-50.
  • Chubinskaya S, Kumar B, Merrihew C, Heretis K, Rueger D, and Kuettner KE. Age-related changes in cartilage endogenous OP-1. Biochimica Biophysica Acta Molecular Basis of Disease. 2002.1588(2):126-34.
  • Loeser RF, Pacione CA, and Chubinskaya S. The combination of insulin-like growth factor 1 and osteogenic protein 1 promotes increased survival of and matrix synthesis by normal and osteoarthritic human chondrocytes. Arthritis and Rheumatism. 2003. 48(8):2188-96.
  • Söder S, Hakimiyan A, Rueger DC, Kuettner KE, Aigner T, Chubinskaya S. Antisense inhibition of osteogenic protein-1 disturbs human articular cartilage integrity. Arthritis and Rheumatism. 2005. 52(2):468-78.
  • Elshaier A, Hakimiyan AA, Rappoport L, Rueger DC, and Chubinskaya S. Effect of interleukin-1b on osteogenic protein-1-induced signaling in adult human articular chondrocytes. Arthritis and Rheumatism. 2009. 60(1):143-54.

Early Cellular Responses in Models of Human Post-Traumatic Osteoarthritis

  • Pascual-Garrido C, Hakimiyan A, Rappoport L, Oegema TR, Wimmer MA, and Chubinskaya S. Anti-apoptotic treatments prevent cartilage degeneration after acute trauma to human ankle cartilage. Osteoarthritis and Cartilage. 2009. 17:1244-51.
  • Anderson DD, Chubinskaya S, Guilak F, Martin JA, Oegema TR, Olson SA, and Buckwalter JA. Post-traumatic osteoarthritis: Improved understanding and opportunities for early intervention. Journal of Orthopedic Research. 2011. 29:802-9.
  • Chubinskaya S and Wimmer MA. Key Pathways to Prevent Post-Traumatic Arthritis for Future Molecule-Based Therapy. Cartilage. 2013. 4(S3):13S-21S.
  • Moran CJ, Pascual-Garrido C, Chubinskaya S, Potter HG, Warren RF, Cole BJ, and Rodeo SA. Restoration of Articular Cartilage: Current Concepts Review. Journal of Bone and Joint Surgery. 2014. 19;96(4): 336-44.
  • Yanke A, Chubinskaya S. The state of cartilage regeneration: current and future technologies. Current Reviews in Musculoskeletal Medicine. 2015. 8(1):108.

Our team

Faculty

  • Susan Chubinskaya, PhD, associate provost of academic affairs; vice-chair, research and faculty development; professor, Department of Pediatrics.
  • Arkady Margulis, MD

Staff

  • Arnavaz Hakimiyan, MS

Contact

For information about current research opportunities, please contact Susan Chubinskaya, PhD. Our main laboratory location is in the Cohn Research Building, 1735 W. Harrison St., Suite 547, Chicago, IL 60612.