Subchondral bone fragility with meniscal tear accelerates and parathyroid hormone decelerates articular cartilage degeneration in rat osteoarthritis model

J Orthop Res. 2018 Jul;36(7):1959-1968. doi: 10.1002/jor.23840. Epub 2018 Jan 16.

Abstract

The aims of this study were to investigate the influence of subchondral bone fragility (SBF) on the progression of the knee osteoarthritis by using a novel rat model, and to examine the preventive effect of parathyroid hormone (PTH) on cartilage degeneration. First, 40 rats were assigned to the following four groups: Sham, SBF, Medial meniscal tear (MMT), and MMT + SBF groups. In SBF and MMT + SBF groups, we induced SBF by microdrilling the subchondral bone. Second, 10 additional rats were randomly assigned to the following two groups: MMT + SBF + saline and MMT + SBF + PTH groups. Osteoarthritic changes in the articular cartilage and subchondral bone were evaluated using safranin-O/fast green staining, matrix metalloproteinase-13 (MMP-13), and type X collagen immunohistochemistry, toluidine blue staining, and micro-CT scanning. The combination of SBF and meniscal tear increased the number of mast cells in the subchondral bone, and led to the abnormal subchondral bone microarchitecture, such as abnormally decreased trabecular number and increased trabecular thickness, compared with meniscal tear alone. Moreover, SBF with meniscal tear enhanced articular cartilage degeneration and increased the expression of MMP-13 and type X collagen, compared with meniscal tear alone. The administration of PTH decreased the number of mast cells in the subchondral bone and improved the microstructural parameters of the subchondral bone, and delayed the progression of articular cartilage degeneration. These results suggest that SBF is one of the factors underlying the osteoarthritis development, especially in knees with traumatic osteoarthritis, and that the administration of PTH is a potential therapeutic treatment for preventing OA progression. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1959-1968, 2018.

Keywords: articular cartilage; cartilage degeneration; osteoarthritis; parathyroid hormone; subchondral bone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Remodeling / drug effects
  • Bone and Bones / metabolism
  • Bone and Bones / pathology*
  • Cartilage / metabolism
  • Cartilage, Articular / metabolism*
  • Collagen Type X / chemistry
  • Disease Models, Animal
  • Disease Progression
  • Hindlimb / pathology
  • Immunohistochemistry
  • Male
  • Mast Cells / metabolism
  • Matrix Metalloproteinase 13 / metabolism
  • Meniscus / injuries
  • Meniscus / pathology*
  • Osteoarthritis / metabolism
  • Osteoarthritis / physiopathology*
  • Parathyroid Hormone / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • X-Ray Microtomography

Substances

  • Collagen Type X
  • Parathyroid Hormone
  • Matrix Metalloproteinase 13
  • Mmp13 protein, rat