E-Poster Presentation 30th Australian and New Zealand Bone and Mineral Society Annual Scientific Meeting 2020

Elevated Levels of active TGFβ1 in the Subchondral Bone Associate with the Severity of Human Osteoarthritis   (#73)

Dzenita Muratovic 1 , David M Findlay 1 , Halimatul Hajimasri 1 , Catherine J.M Stapledon 1 , Yea-Rin Lee 1 , Julia S Kuliwaba 1
  1. Centre for Orthopaedic & Trauma Research, The University of Adelaide, Adelaide, South Australia, Australia

Introduction

Over-activity of transforming growth factor beta (TGFβ1) in subchondral bone has a direct causal role in rodent knee osteoarthritis (OA) which can be blocked by TGFβ neutralisation. The aim of this study was to investigate whether the level of active TGFβ protein in the subchondral bone associates with the structural, cellular and molecular parameters that are characteristic of human knee OA.

Methods 

Tibial plateaus were collected from 35 knee OA arthroplasty patients (15 men, aged 66±9 years; 20 women, aged 70±8 years). Subchondral trabecular bone was sampled from regions below macroscopically present cartilage (CA+) and regions with denuded cartilage (CA-). Bone samples were processed for ELISA measurement of active and total TGFβ1 protein concentration and gene-specific mRNA expression by RT-PCR, synchrotron micro-CT imaging to obtain bone quality parameters (Figure 1), and histology to determine OARSI grade, osteocyte density and TRAP+ cell density.

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Results

Bone samples collected below CA- regions (mean OARSI=6) had increased concentration of active TGFβ1 protein and RANKL/OPG mRNA ratio compared to bone samples from CA+ regions (mean OARSI=3.3). Subchondral bone from CA- regions was characterised by sclerotic microarchitecture, increased bone mineral density, increased osteocyte and TRAP+ cell density, larger and greater numbers of osteocyte lacunae that were less spherical shape, and increased bone marrow and bone matrix vascular density. Further, OARSI grade positively associated with active/total TGFβ1 ratio, total TRAP+ cell density, osteocyte density, lacunar volume and shape, and  bone marrow and bone matrix vascular density.

Discussion

Together, these findings suggest regional cellular and molecular mechanisms involved in bone remodelling in human knee OA. Further, increased concentration of active TGFβ in the subchondral bone closely associates with impaired overall bone quality and the severity of human OA. Importantly these findings may open up new options for therapeutic approaches for human OA, through the inhibition of TGFβ1.