Subchondral Cellular Density Decreases with Increasing Grade of Cartilage Degeneration in Knee Osteoarthritis - An Ex Vivo Histopathological Analysis

Overview

Journal J Orthop Case Rep

Specialty Orthopedics

Date 2025 Feb 17

PMID 39957951

Authors

Sathish Muthu

Ragavi Kandasamy

Suryaprabha Palanisamy

Arun Anand Palaniappan

Affiliations

Soon will be listed here.

Abstract

Introduction: Subchondral milieu has been the region of interest in recent clinical trials demonstrating it as an effective treatment focus in knee osteoarthritis (OA). However, a systematic analysis of the subchondral cell population density is lacking in knee OA. Hence, this study aims to analyze the cell population density of the subchondral zone for every stage of cartilage degeneration to analyze the rationale behind this evolving treatment method for knee OA.

Materials And Methods: This is an ex vivo histopathological analysis of the distal femur and proximal tibia articular specimens from the patients undergoing total knee replacement for primary knee OA between November 2023 and March 2024. Two pathologists independently graded and analyzed the subchondral cell density based on the International Cartilage Repair Society cartilage injury grading system.

Results: We noted a significant association between the grade of cartilage degeneration and the subchondral cell density (r = 0.831, P < 0.001). We noted a statistically significant decrease in the cell density for every stage of cartilage injury compared to the control (P < 0.001). We also noted a significant decrease in cell density between the early and late stages of cartilage degeneration (P < 0.001). We did not note any significant difference in the cell density between the tibial and femoral articular cartilage for every grade of cartilage degeneration analyzed (P = 0.432).

Conclusion: Subchondral cell density decreases significantly with increasing grade of degeneration in knee OA. Subchondral milieu warrants attention to be considered as a potential treatment focus that could alter the disease progression in knee OA.

References

Goldring M, Goldring S . Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis. Ann N Y Acad Sci. 2010; 1192:230-7. DOI: 10.1111/j.1749-6632.2009.05240.x. View

Jones E, Crawford A, English A, Henshaw K, Mundy J, Corscadden D . Synovial fluid mesenchymal stem cells in health and early osteoarthritis: detection and functional evaluation at the single-cell level. Arthritis Rheum. 2008; 58(6):1731-40. DOI: 10.1002/art.23485. View

Hu Y, Chen X, Wang S, Jing Y, Su J . Subchondral bone microenvironment in osteoarthritis and pain. Bone Res. 2021; 9(1):20. PMC: 7969608. DOI: 10.1038/s41413-021-00147-z. View

Sekiya I, Ojima M, Suzuki S, Yamaga M, Horie M, Koga H . Human mesenchymal stem cells in synovial fluid increase in the knee with degenerated cartilage and osteoarthritis. J Orthop Res. 2011; 30(6):943-9. DOI: 10.1002/jor.22029. View

Hugle T, Geurts J . What drives osteoarthritis?-synovial versus subchondral bone pathology. Rheumatology (Oxford). 2016; 56(9):1461-1471. DOI: 10.1093/rheumatology/kew389. View

Tjandra K, Novriansyah R, Sudiasa I, Ar A, Rahmawati N, Dilogo I . Modified Mesenchymal stem cell, platelet-rich plasma, and hyaluronic acid intervention in early stage osteoarthritis: A systematic review, meta-analysis, and meta-regression of arthroscopic-guided intra-articular approaches. PLoS One. 2024; 19(3):e0295876. PMC: 10923406. DOI: 10.1371/journal.pone.0295876. View

Neogi T, Nevitt M, Niu J, Sharma L, Roemer F, Guermazi A . Subchondral bone attrition may be a reflection of compartment-specific mechanical load: the MOST Study. Ann Rheum Dis. 2009; 69(5):841-4. PMC: 2891513. DOI: 10.1136/ard.2009.110114. View

Henrotin Y, Pesesse L, Sanchez C . Subchondral bone in osteoarthritis physiopathology: state-of-the art and perspectives. Biomed Mater Eng. 2010; 19(4-5):311-6. DOI: 10.3233/BME-2009-0596. View

Ding J, Hu K . Injectable therapies for knee osteoarthritis. Reumatologia. 2021; 59(5):330-339. PMC: 8609383. DOI: 10.5114/reum.2021.110612. View

10.

Muratovic D, Findlay D, Cicuttini F, Wluka A, Lee Y, Edwards S . Bone marrow lesions in knee osteoarthritis: regional differences in tibial subchondral bone microstructure and their association with cartilage degeneration. Osteoarthritis Cartilage. 2019; 27(11):1653-1662. DOI: 10.1016/j.joca.2019.07.004. View

11.

Pan J, Zhou X, Li W, Novotny J, Doty S, Wang L . In situ measurement of transport between subchondral bone and articular cartilage. J Orthop Res. 2009; 27(10):1347-52. PMC: 2748158. DOI: 10.1002/jor.20883. View

12.

Hernigou P, Auregan J, Dubory A, Flouzat-Lachaniette C, Chevallier N, Rouard H . Subchondral stem cell therapy versus contralateral total knee arthroplasty for osteoarthritis following secondary osteonecrosis of the knee. Int Orthop. 2018; 42(11):2563-2571. DOI: 10.1007/s00264-018-3916-9. View

13.

Keeling L, Belk J, Kraeutler M, Kallner A, Lindsay A, McCarty E . Bone Marrow Aspirate Concentrate for the Treatment of Knee Osteoarthritis: A Systematic Review. Am J Sports Med. 2021; 50(8):2315-2323. DOI: 10.1177/03635465211018837. View

14.

Hernigou P, Bouthors C, Bastard C, Flouzat Lachaniette C, Rouard H, Dubory A . Subchondral bone or intra-articular injection of bone marrow concentrate mesenchymal stem cells in bilateral knee osteoarthritis: what better postpone knee arthroplasty at fifteen years? A randomized study. Int Orthop. 2020; 45(2):391-399. DOI: 10.1007/s00264-020-04687-7. View

15.

Chahla J, Piuzzi N, Mitchell J, Dean C, Pascual-Garrido C, LaPrade R . Intra-Articular Cellular Therapy for Osteoarthritis and Focal Cartilage Defects of the Knee: A Systematic Review of the Literature and Study Quality Analysis. J Bone Joint Surg Am. 2016; 98(18):1511-21. DOI: 10.2106/JBJS.15.01495. View

16.

Yusup A, Kaneko H, Liu L, Ning L, Sadatsuki R, Hada S . Bone marrow lesions, subchondral bone cysts and subchondral bone attrition are associated with histological synovitis in patients with end-stage knee osteoarthritis: a cross-sectional study. Osteoarthritis Cartilage. 2015; 23(11):1858-64. DOI: 10.1016/j.joca.2015.05.017. View

17.

Jeyaraman M, Muthu S, Jeyaraman N, Ranjan R, Jha S, Mishra P . Synovium Derived Mesenchymal Stromal Cells (Sy-MSCs): A Promising Therapeutic Paradigm in the Management of Knee Osteoarthritis. Indian J Orthop. 2022; 56(1):1-15. PMC: 8748553. DOI: 10.1007/s43465-021-00439-w. View

18.

Muthu S, Korpershoek J, Novais E, Tawy G, Hollander A, Martin I . Failure of cartilage regeneration: emerging hypotheses and related therapeutic strategies. Nat Rev Rheumatol. 2023; 19(7):403-416. DOI: 10.1038/s41584-023-00979-5. View

19.

Kasaeian A, Roemer F, Ghotbi E, Ibad H, He J, Wan M . Subchondral bone in knee osteoarthritis: bystander or treatment target?. Skeletal Radiol. 2023; 52(11):2069-2083. DOI: 10.1007/s00256-023-04422-4. View

20.

Muthu S . Osteoarthritis, an old wine in a new bottle!. World J Orthop. 2023; 14(1):1-5. PMC: 9850792. DOI: 10.5312/wjo.v14.i1.1. View