Role of Subchondral Bone in the Initiation and Progression of Cartilage Damage

Radin, Eric L.; Rose, Robert M.

doi:10.1097/00003086-198612000-00005

Cited by 827 publications

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“…As mentioned above, some studies have indicated that subchondral bone changes precede and may be responsible for the evolution of cartilage lesions [29,95,96]. Others have indicated that subchondral bone changes would only be secondary to cartilage degradation [97,98].…”

Section: Interaction Between Subchondral Bone and Cartilagementioning

confidence: 99%

Targeting subchondral bone for treating osteoarthritis: what is the evidence?

Tat

Lajeunesse

Pelletier

et al. 2010

Best Practice & Research Clinical Rheumatology

156

121

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Over the past few decades, significant progress has been made with respect to new concepts about the pathogenesis of osteoarthritis (OA). This article summarises some of the knowledge we have today on the involvement of the subchondral bone in OA. It provides substantial evidence that changes in the metabolism of the subchondral bone are an integral part of the OA disease process and that these alterations are not merely secondary manifestations, but are part of a more active component of the disease. Thus, a strong rationale exists for therapeutic approaches that target subchondral bone resorption and/or formation, and data evaluating the drugs targeting bone remodelling raise the hope that new treatment options for OA may become available.

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Section: Interaction Between Subchondral Bone and Cartilagementioning

confidence: 99%

Targeting subchondral bone for treating osteoarthritis: what is the evidence?

Tat

Lajeunesse

Pelletier

et al. 2010

Best Practice & Research Clinical Rheumatology

156

121

View full text Add to dashboard Cite

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“…Whether the trabecular changes of the bone precede or follow the changes in the cartilage is unknown, but the bony changes are considered necessary for the progression of OA [6]. It has even been postulated that the bony changes may precede the cartilage degeneration [30]. Before the changes with OA can be completely understood, though, a thorough understanding of normal bone structure and variation with compartment and depth is certainly necessary.…”

Section: Introductionmentioning

confidence: 99%

MicroCT evaluation of normal and osteoarthritic bone structure in human knee specimens

Patel

Issever

Burghardt

et al. 2003

Journal Orthopaedic Research

116

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Although trabecular bone structure has been evaluated, variation with knee compartment and depth from joint surface is not completely understood. Cadaver knees were evaluated with microcomputed tomography analysis for these variations. Objective differences were compared between: medial vs. lateral compartments; femoral vs. tibial bone; and normal vs. arthritic knees. Depth dependent changes in the parameters were observed for the first 6 mm of the cores in normal knees: BV/TV, Tb.N and Conn.D gradually decrease, while Tb.Sp and SMI increase. In the first 6 mm of the normal tibia BV/TV, Tb.N, and Tb.Th are greater than in the femur on both the medial and lateral compartments while Tb.Sp, SMI, and C0nn.D are lower. The medial compartment values for BV/TV, Tb.N, Tb.Th and C0nn.D are generally greater than for the lateral in both the femur and tibia while Tb.Sp and SMI are lower. In comparison of normal vs. arthritic knees significant differences are observed in the first 6 mm of the medial tibia. With arthritis BV/TV and Tb.Th are lower, while SMI and Tb.Sp are higher. Tb.N and C0nn.D show no statistically significant difference. The bone structure variations are, thus, most prominent in the first 6 mm of depth and medial compartment bone is generally more structurally sound than lateral. Severely arthritic bone changes are most prominent in the medial compartment of the tibia and bone structure is less sound in severe arthritis.

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“…More than 30 years ago, Radin et al (10,11) suggested that changes in bone might be a cause of OA. Since that time, there has been substantial evidence that changes in the metabolism of bone, particularly in the area of the subchondral bone, are an integral part of the disease (12)(13)(14)(15)(16)(17)(18). Recent studies, however, point to the fact that the fate of articular cartilage is not determined exclusively by stiffening (sclerosis) of subchondral bone, but rather, by a remodeling of this tissue (19,20).…”

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confidence: 99%

Activation of the receptor EphB4 by its specific ligand ephrin B2 in human osteoarthritic subchondral bone osteoblasts

Tat¹,

Pelletier²,

Amiable³

et al. 2008

Arthritis & Rheumatism

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Objective. Abnormal subchondral bone metabolism is involved in osteoarthritis (OA). It has been suggested that ephrin B2 and its specific receptor EphB4 participate in bone homeostasis. We previously reported that human OA subchondral bone osteoblasts could be classified into 2 subpopulations: low (L), having proresorption properties, and high (H), having proformation properties. The purpose of this study was to investigate the importance of the ephrin system in OA subchondral bone osteoblasts.Methods. The presence of the EphB4 receptor was determined by immunohistochemistry, and its expression level, modulation upon treatment, and consequences of activation by ephrin B2 were determined by quantitative polymerase chain reaction. The effects of ephrin B2 activation of the EphB4 receptor on bone resorption activity were also determined. EphB4 receptor activation signaling pathways were investigated by specific enzyme-linked immunosorbent assay.Results. EphB4 receptors were present in subchondral bone osteoblasts and osteocytes. Compared with normal and H-OA osteoblasts, EphB4 receptor expression levels were significantly increased in L-OA osteoblasts, with no difference between normal and H-OA osteoblasts. EphB4 receptor levels in L-OA osteoblasts were significantly up-regulated by prostaglandin E 2 (PGE 2 ) and interleukin-17 (IL-17). Ephrin B2, PGE 2 , and IL-17 significantly inhibited bone resorption activity in these cells. EphB4 activation by ephrin B2 significantly inhibited the expression of IL-1␤, IL-6, matrix metalloproteinase 1 (MMP-1), MMP-9, MMP-13, and RANKL, but not MMP-2 and osteoprotegerin. EphB4 receptor activation significantly inhibited the phosphatidylinositol 3-kinase/Akt pathway.Conclusion. This study is the first to provide evidence that EphB4 receptor activation by ephrin B2 in OA subchondral bone could affect abnormal metabolism in this tissue by inhibiting resorption factors and their activities. Ephrin B2 could be targeted as a specific therapeutic approach in the development of a diseasemodifying OA drug.Subchondral bone is made up of a specialized connective tissue formed by a mineralized matrix containing the specific type I collagen, proteoglycans, and several growth factors and cytokines, as well as bonespecific cell types (osteoblasts, osteocytes, and osteoclasts) (1,2). Osteoblast and osteoclast activities, either alone or in combination, contribute to the bone remodeling process, and any disturbance in the activities of these 2 cells is responsible for the development of altered bone metabolism.The ephrin B molecules (ephrin B1, ephrin B2, and ephrin B3) bind in a specific manner to their EphB

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Role of Subchondral Bone in the Initiation and Progression of Cartilage Damage

Cited by 827 publications

References 0 publications

Targeting subchondral bone for treating osteoarthritis: what is the evidence?

Targeting subchondral bone for treating osteoarthritis: what is the evidence?

MicroCT evaluation of normal and osteoarthritic bone structure in human knee specimens

Activation of the receptor EphB4 by its specific ligand ephrin B2 in human osteoarthritic subchondral bone osteoblasts

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