Co-expression of DKK-1 and Sclerostin in Subchondral Bone of the Proximal Femoral Heads from Osteoarthritic Hips

Allahdad Zarei,M Kassim Javaid,Philippa A Hulley,Afsie Sabokbar

doi:10.1007/s00223-017-0246-7

Allahdad Zarei, M Kassim Javaid + Show 2 more

Open Access

https://doi.org/10.1007/s00223-017-0246-7

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Abstract

BackgroundOsteoarthritis (OA) is a progressively degenerative joint disease influenced by structural and metabolic factors. There is growing evidence that subchondral bone is involved in both symptomatic and structural progression in OA. The Wnt pathway has been implicated in the progression of OA but the expression and function of the Wnt inhibitors, Dikkopf (DKK-1) and sclerostin (SOST), are unclear.MethodsWe examined the regional distribution of DKK-1 and SOST in subchondral bone of the femoral head using resection specimens following arthroplasty in patients presenting with end-stage OA. Cylindrical cores for immunohistochemistry were taken through midpoint of full thickness cartilage defect, partial cartilage defect, through base of osteophyte and through macroscopically normal cartilage.ResultsSubchondral bone was thickest in cores taken from regions with full cartilage defect and thinnest in cores taken from osteophyte regions. In subchondral bone, expression of both DKK-1 and SOST was observed exclusively in osteocytes. Expression was highest in subchondral bone in cores taken from regions with partial but not full thickness cartilage defects. DKK-1 but not SOST was expressed by chondrocytes in cores with macroscopically normal cartilage.ConclusionThe current study describes the regional cellular distribution of SOST and DKK-1 in hip OA. Expression was highest in the osteocytes in bone underlying partial thickness cartilage defects. It is however not clear if this is a cause or a consequence of alterations in the overlying cartilage. However, it is suggestive of an active remodeling process which might be targeted by disease-modifying agents.

Highlights

Osteoarthritis (OA) is a progressively degenerative joint disease influenced by structural and metabolic factors
In an attempt to identify whether the presence or absence of cartilage, partial cartilage defect or presence of osteophytes would affect the thickness of the subchondral plate the structural parameters of subchondral bone plate were evaluated (Fig. 1a–e)
When OA femoral head cores were examined for DKK-1 immunoreactivity, surface chondrocytes in macroscopically normal cartilage regions (Fig. 2d, blue arrows) expressed abundant DKK-1

Summary

Introduction

Osteoarthritis (OA) is a progressively degenerative joint disease influenced by structural and metabolic factors. There is growing evidence that subchondral bone is involved in both symptomatic and structural progression in OA. Expression of both DKK-1 and SOST was observed exclusively in osteocytes. Expression was highest in subchondral bone in cores taken from regions with partial but not full thickness cartilage defects. There is a growing body of evidence demonstrating changes in the architecture in subchondral bone underlying OA cartilage lesions, which may contribute to the pathogenesis of both structural and symptomatic features of OA [1]. OA is a disease involving cartilage damage, changes in underlying subchondral bone, osteophyte formation, and inflammation of the joint with unknown factors that initiate these changes [6]. The search for other factors that may be involved in cartilage degradation accompanied by alterations in underlying bone has introduced new directions for investigations focused on signaling pathways such

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