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Evaluation of in vitro growth factor treatments on fibrochondrogenesis by synovial membrane cells from osteoarthritic and nonosteoarthritic joints of dogs

Jennifer J. Warnock DVM, PhD1, Derek B. Fox DVM, PhD2, Aaron M. Stoker PhD3, and James L. Cook DVM, PhD4
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  • 1 Comparative Orthopaedic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.
  • | 2 Comparative Orthopaedic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.
  • | 3 Comparative Orthopaedic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.
  • | 4 Comparative Orthopaedic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.

Abstract

Objective—To determine the in vitro effects of selected growth factors on fibrochondrogenesis by synovial membrane cells from nonosteoarthritic (normal) and osteoarthritic joints of dogs.

Animals—5 dogs with secondary osteoarthritis of shoulder or stifle joints and 6 dogs with normal joints.

Procedures—Synovial membrane cells were harvested from normal and osteoarthritic joints and cultured in monolayer with or without (control) basic fibroblast growth factor, transforming growth factor-β1, and insulin-like growth factor-1. In the cultured cells, fibrochondrogenesis was measured by use of a real-time reverse transcriptase PCR assay to determine relative expressions of collagen I, collagen II, and aggrecan genes and of 3 genes involved in embryonic chondrogenesis: Sry-type homeobox protein-9 (SOX-9), frizzled-motif associated with bone development (Frzb), and regulator of G-protein signaling-10 (RGS-10). Tissue collagen content was measured via a hydroxyproline assay, and sulfated glycosaminoglycan content was measured via a 1,9-dimethylmethylene blue assay. Cellularity was determined via a double-stranded DNA assay. Immunohistochemical analysis for collagens I and II was also performed.

Results—In vitro collagen synthesis was enhanced by growth factor stimulation. Although osteoarthritic-joint synoviocytes could undergo a fibrocartilage-like phenotypic shift, their production of collagenous extracellular matrix was less than that of normal-joint synoviocytes. Gene expressions of SOX-9 and RGS-10 were highest in the osteoarthritic-joint cells; Frzb expression was highest in growth factor treated cells.

Conclusions and Clinical Relevance—Autogenous synovium may be a viable cell source for meniscal tissue engineering. Gene expressions of SOX-9 and RGS-10 may be potential future targets for in vitro enhancement of chondrogenesis.

Contributor Notes

Address correspondence to Dr. Warnock (jennifer.warnock@oregonstate.edu).

Dr. Warnock's present address is Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331.

This manuscript represents a portion of a dissertation submitted by the first author to the Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, as partial fulfillment of the requirements for a Doctor of Philosophy degree.

Supported by the Veterinary Orthopedic Society Hohn-Johnson Research Grant and the Comparative Orthopaedic Laboratory.

Presented in part as an oral presentation at the Veterinary Orthopedic Society Conference, Big Sky, Mont, March 2008.