Skip to main content

Emerging Concepts of Endotypes/Phenotypes in Regenerative Medicine for Osteoarthritis

Abstract

Osteoarthritis (OA) represents a broad spectrum of different conditions. Our present understanding of phenotypes and endotypes can explain the differences in clinical manifestations, etiology, and underlying pathophysiology. Although this concept was first applied in choosing the right target population for clinical trials of disease-modifying osteoarthritis drugs (DMOADs), given that the regenerative medicine so far has not delivered uniformly successful results in structural improvement in OA, it merits a consideration to introduce the concept of phenotype/endotype in the regenerative medicine for OA toward an effort to find the right patients for these expensive therapeutics. A better understanding of molecular endotypes facilitates defining clinical phenotypes more clearly. Based on this knowledge, these patients may respond better to treatments that can preserve joints, including regenerative medicine. On the other hand, patients who are not expected to benefit from these treatments may receive earlier total joint replacement surgery. This will result in a reduction of healthcare costs, as well as a more effective approach to new drug development. An understanding of phenotypes/endotypes will contribute to the selection of suitable patients for regenerative treatment of OA.

This is a preview of subscription content, access via your institution.

References

  1. 1.

    Sander M, Oxlund B, Jespersen A, Krasnik A, Mortensen EL, Westendorp RG, et al. The challenges of human population ageing. Age Ageing. 2015;44:185–7.

    Article  Google Scholar 

  2. 2.

    Collins KH, Herzog W, MacDonald GZ, Reimer RA, Rios JL, Smith IC, et al. Obesity, metabolic syndrome, and musculoskeletal disease: common inflammatory pathways suggest a central role for loss of muscle integrity. Front Physiol. 2018;9:112.

    Article  Google Scholar 

  3. 3.

    Mobasheri A, van Spil WE, Budd E, Uzieliene I, Bernotiene E, Bay-Jensen AC, et al. Molecular taxonomy of osteoarthritis for patient stratification, disease management and drug development: biochemical markers associated with emerging clinical phenotypes and molecular endotypes. Curr Opin Rheumatol. 2019;31:80–9.

    Article  Google Scholar 

  4. 4.

    Goldring MB, Goldring SR. Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis. Ann N Y Acad Sci. 2010;1192:230–7.

    CAS  Article  Google Scholar 

  5. 5.

    Murray CJ, Lopez AD. The global burden of disease: a comprehensive assessment of mortality and disability from disease, injuries and risk factors in 1990 and projected to 2020. Boston: Harvard University Press; 1996.

    Google Scholar 

  6. 6.

    Smith TM, Tafforeau P, Reid DJ, Grün R, Eggins S, Boutakiout M, et al. Earliest evidence of modern human life history in North African early Homo sapiens. Proc Natl Acad Sci U S A. 2007;104:6128–33.

    CAS  Article  Google Scholar 

  7. 7.

    Im GI. Perspective on intra-articular injection cell therapy for osteoarthritis treatment. Tissue Eng Regen Med. 2019;16:357–63.

    CAS  Article  Google Scholar 

  8. 8.

    Im GI. Current status of regenerative medicine in osteoarthritis. Bone Joint Res. 2021;10:134–6.

    Article  Google Scholar 

  9. 9.

    Kim MK, Ha CW, In Y, Cho SD, Choi ES, Ha JK, et al. A multicenter, double-blind, phase III clinical trial to evaluate the efficacy and safety of a cell and gene therapy in knee osteoarthritis patients. Hum Gene Ther Clin Dev. 2018;29:48–59.

    CAS  Article  Google Scholar 

  10. 10.

    Ko JY, Park JW, Kim J, Im GI. Characterization of adipose-derived stromal/stem cell spheroids versus single-cell suspension in cell survival and arrest of osteoarthritis progression. J Biomed Mater Res A. 2021;109:869–78.

    Article  Google Scholar 

  11. 11.

    Van Spil WE, Kubassova O, Boesen M, Bay-Jensen AC, Mobasheri A. Osteoarthritis phenotypes and novel therapeutic targets. Biochem Pharmacol. 2019;165:41–8.

    CAS  Article  Google Scholar 

  12. 12.

    Berenbaum F. Deep phenotyping of osteoarthritis: a step forward. Ann Rheum Dis. 2019;78:3–5.

    Article  Google Scholar 

  13. 13.

    Kraus VB, Blanco FJ, Englund M, Karsdal MA, Lohmander LS. Call for standardized definitions of osteoarthritis and risk stratification for clinical trials and clinical use. Osteoarthritis Cartilage. 2015;23:1233–41.

    CAS  Article  Google Scholar 

  14. 14.

    Kuruvilla ME, Lee FE, Lee GB. Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol. 2018;56:219–33.

    Article  Google Scholar 

  15. 15.

    Bierma-Zeinstra SM, van Middelkoop M. Osteoarthritis: in search of phenotypes. Nat Rev Rheumatol. 2017;13:705–6.

    Article  Google Scholar 

  16. 16.

    Nevins JR, Potti A. Mining gene expression profiles: expression signatures as cancer phenotypes. Nat Rev Genet. 2007;8:601–9.

    CAS  Article  Google Scholar 

  17. 17.

    Leyland KM, Hart DJ, Javaid MK, Judge A, Kiran A, Soni A, et al. The natural history of radiographic knee osteoarthritis: a fourteen-year population-based cohort study. Arthritis Rheum. 2012;64:2243–51.

    CAS  Article  Google Scholar 

  18. 18.

    Dell’Isola A, Steultjens M. Classification of patients with knee osteoarthritis in clinical phenotypes: data from the osteoarthritis initiative. PLoS One. 2018;13:e0191045.

    Article  Google Scholar 

  19. 19.

    Mobasheri A, Rayman MP, Gualillo O, Sellam J, van der Kraan P, Fearon U. The role of metabolism in the pathogenesis of osteoarthritis. Nat Rev Rheumatol. 2017;13:302–11.

    CAS  Article  Google Scholar 

  20. 20.

    Mobasheri A, Saarakkala S, Finnilä M, Karsdal MA, Bay- Jensen AC, van Spil WE. Recent advances in understanding the phenotypes of osteoarthritis. F1000Res. 2019;8:F1000 Faculty Rev-2091.

  21. 21.

    Petersen KK, Olesen AE, Simonsen O, Arendt-Nielsen L. Mechanistic pain profiling as a tool to predict the efficacy of 3-week nonsteroidal anti-inflammatory drugs plus paracetamol in patients with painful knee osteoarthritis. Pain. 2019;160:486–92.

    CAS  Article  Google Scholar 

Download references

Acknowledgment

Funding was provided by National Research Foundation of Korea (Grant No. NRF-2020R1A2C2008266).

Author information

Affiliations

Authors

Corresponding author

Correspondence to Gun-Il Im.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

There are no animal experiments carried out for this .

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Im, GI., Moon, JY. Emerging Concepts of Endotypes/Phenotypes in Regenerative Medicine for Osteoarthritis. Tissue Eng Regen Med (2021). https://doi.org/10.1007/s13770-021-00397-2

Download citation

Keywords

  • Endotypes/phenotypes
  • Regenerative medicine
  • Osteoarthritis