Targeted In Situ Biosynthetic Transcriptional Activation in Native Surface-Level Human Articular Chondrocytes during Lesion Stabilization

Kumkum Ganguly; Ian D McRury; Peter M Goodwin; Roy E Morgan; Wayne K Augé 2nd

doi:10.1177/1947603511426881

Targeted In Situ Biosynthetic Transcriptional Activation in Native Surface-Level Human Articular Chondrocytes during Lesion Stabilization

Cartilage. 2012 Apr;3(2):141-55. doi: 10.1177/1947603511426881.

Authors

Kumkum Ganguly¹, Ian D McRury², Peter M Goodwin¹, Roy E Morgan², Wayne K Augé 2nd³

Affiliations

¹ Los Alamos National Laboratory, Los Alamos, NM, USA.
² NuOrtho Surgical Inc., Fall River, MA, USA.
³ NuOrtho Surgical Inc., Fall River, MA, USA ; Center for Orthopaedic and Sports Performance Research Inc., Santa Fe, NM, USA.

Abstract

Objective: Safe articular cartilage lesion stabilization is an important early surgical intervention advance toward mitigating articular cartilage disease burden. While short-term chondrocyte viability and chondrosupportive matrix modification have been demonstrated within tissue contiguous to targeted removal of damaged articular cartilage, longer term tissue responses require evaluation to further clarify treatment efficacy. The purpose of this study was to examine surface chondrocyte responses within contiguous tissue after lesion stabilization.

Methods: Nonablation radiofrequency lesion stabilization of human cartilage explants obtained during knee replacement was performed for surface fibrillation. Time-dependent chondrocyte viability, nuclear morphology and cell distribution, and temporal response kinetics of matrix and chaperone gene transcription indicative of differentiated chondrocyte function were evaluated in samples at intervals to 96 hours after treatment.

Results: Subadjacent surface articular cartilage chondrocytes demonstrated continued viability for 96 hours after treatment, a lack of increased nuclear fragmentation or condensation, persistent nucleic acid production during incubation reflecting cellular assembly behavior, and transcriptional up-regulation of matrix and chaperone genes indicative of retained biosynthetic differentiated cell function.

Conclusions: The results of this study provide further evidence of treatment efficacy and suggest the possibility to manipulate or induce cellular function, thereby recruiting local chondrocytes to aid lesion recovery. Early surgical intervention may be viewed as a tissue rescue, allowing articular cartilage to continue displaying biological responses appropriate to its function rather than converting to a tissue ultimately governed by the degenerative material property responses of matrix failure. Early intervention may positively impact the late changes and reduce disease burden of damaged articular cartilage.

Keywords: arthroscopy < procedures; articular cartilage < tissue; cartilage repair < repair; chondrocytes < cells; gene therapy < therapeutic delivery.