Chondrocytes respond both anabolically and catabolically to impact loading generally considered non-injurious

Stephany Santos; Kelsey Richard; Melanie C Fisher; Caroline N Dealy; David M Pierce

doi:10.1016/j.jmbbm.2020.104252

Chondrocytes respond both anabolically and catabolically to impact loading generally considered non-injurious

J Mech Behav Biomed Mater. 2021 Mar:115:104252. doi: 10.1016/j.jmbbm.2020.104252. Epub 2020 Dec 17.

Authors

Stephany Santos¹, Kelsey Richard², Melanie C Fisher³, Caroline N Dealy⁴, David M Pierce⁵

Affiliations

¹ Department of Biomedical Engineering, University of Connecticut, Storrs, CT, United States of America.
² Department of Global Health, University of Connecticut, Storrs, CT, United States of America.
³ Center for Regenerative Medicine and Skeletal Development, Department of Reconstructive Services, University of Connecticut Health Center, Farmington, CT, United States of America.
⁴ Center for Regenerative Medicine and Skeletal Development, Department of Reconstructive Services, University of Connecticut Health Center, Farmington, CT, United States of America; Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT, United States of America.
⁵ Department of Biomedical Engineering, University of Connecticut, Storrs, CT, United States of America; Department of Mechanical Engineering, University of Connecticut, Storrs, CT, United States of America. Electronic address: dmpierce@engr.uconn.edu.

PMID: 33385951
DOI: 10.1016/j.jmbbm.2020.104252

Abstract

We aimed to determine the longitudinal effects of low-energy (generally considered non-injurious) impact loading on (1) chondrocyte proliferation, (2) chondroprogenitor cell activity, and (3) EGFR signaling. In an in vitro study, we assessed 127 full-thickness, cylindrical osteochondral plugs of bovine cartilage undergoing either single, uniaxial unconfined impact loads with energy densities in the range of 1.5-3.2mJ/mm³ or no impact (controls). We quantified cell responses at two, 24, 48, and 72 h via immunohistochemical labeling of Ki67, Sox9, and pEGFR antibodies. We compared strain, stress, and impact energy density as predictors for mechanotransductive responses from cells, and fit significant correlations using linear regressions. Our study demonstrates that low-energy mechanical impacts (1.5-3.2mJ/mm³) generally stimulate time-dependent anabolic responses in the superficial zone of articular cartilage and catabolic responses in the middle and deep zones. We also found that impact energy density is the most consistent predictor of cell responses to low-energy impact loading. These spatial and temporal changes in chondrocyte behavior result directly from low-energy mechanical impacts, revealing a new level of mechanotransductive sensitivity in chondrocytes not previously appreciated.

Keywords: Articular cartilage; EGFR; Ki67; Mechanical impact; Metabolism; Progenitor; Sox9.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Cartilage, Articular*
Cattle
Chondrocytes*
Signal Transduction
Stress, Mechanical