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SAT0485 Increased expression of osteoprotegerin in CD271+ multipotential stromal cells from femoral heads of patients with hip osteoarthritis
  1. DC Ilas1,
  2. SM Churchman1,
  3. J Aderinto2,
  4. PV Giannoudis1,
  5. D McGonnagle1,
  6. E Jones1
  1. 1Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds
  2. 2Department of Orthopaedics, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom

Abstract

Background Osteoarthritis is a disease of the whole joint, but subchodral bone marrow lesions (BMLs) closely correlate with disease progression [1]. We have previously shown that in OA femoral heads, subchondral bone multipotential stromal cells (MSCs) were 5-fold more abundant in MRI determined BML areas where they also showed reduced mineralisation capacity and altered RANKL expression compared to non-BML areas [2]. This offered novel insight into MSC involvement in the bone remodeling process in OA.

Objectives The current study investigated a multi-lineage gene expression profile of native CD271+ MSCs from OA femoral heads focusing on osteogenesis and bone remodeling related genes compared to CD271+ MSCs from healthy trabecular bone.

Methods Femoral heads were obtained from 17 OA patients undergoing total hip arthroplasty. Control samples included healthy iliac crest bone from 12 patients undergoing autograft harvesting for bone reconstruction and healthy femoral neck bone from 2 patients, extracted following core decompression surgery for avascular necrosis of the femoral head. CD271+ MSCs were extracted by enzymatic digestion and purified by FACS, as previously described [3, 4]. MSC cultures were generated by standard methods [4]. Quantitative real-time PCR was performed using TaqMan assays for 12 transcripts and gene expression was normalised to HPRT1.

Results Sorted CD271+ cells from both groups displayed gene expression profiles indicative of their steady-state osteogenic, adipogenic, bone remodeling and stromal-support functions (Table 1). Three out of 11 transcripts showed significant increases in OA: alkaline phosphatase, melanoma cell adhesion molecule and osteoprotegerin (OPG) (p<0.05, Mann Whitney test). The proportion of CD271+ cells in relation to total live cells was more variable but on average 2-fold higher in OA (medians of 2.3 and 5.2%, respectively, not significant). Consistent with previous findings [4, 5], gene expression levels for the majority of transcripts were altered following MSC culture expansion (3 up-regulated and 8 down-regulated).

Conclusions This is the first study to show gene expression alterations in uncultured CD271+ MSCs from OA patients. A notable increase in OPG is suggestive of MSCs' bias towards inhibition of bone resorption in late hip OA and further incriminates the RANKL/OPG pathway, specifically in MSCs, in OA pathophysiology. Further studies are needed to define the role of native MSCs in lesion associated OA disease progression and to evaluate these as a possible target for treatment.

References

  1. Goldring et al, Nat Rev Rheumatol. 2016;12:632.

  2. Campbell et al, Arthritis Rheumatol. 2016;68:1648-.

  3. Jones et al., Arthritis Rheum. 2010 Jul;62:1944.

  4. Churchman et al., Arthritis Rheum. 2012 Aug;64:2632.

  5. Churchman et al., Stem Cells Int, 2017 (in press).

References

Disclosure of Interest None declared

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