Calcium-phosphate complex increased during subchondral bone remodeling affects earlystage osteoarthritis

An activation of osteoclasts and subchondral bone remodeling is a major histologic feature of early-stage osteoarthritis (OA), which can be accompanied by an increase of calcium (Ca) and phosphate (Pi) level in the subchondral milieu. Considering articular cartilage gets most of nutrition from subch...

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Bibliographic Details
Published in:	Scientific reports 2018-01, Vol.8 (1), p.487-487, Article 487
Main Authors:	Jung, Youn-Kwan, Han, Min-Su, Park, Hye-Ri, Lee, Eun-Ju, Jang, Ji-Ae, Kim, Gun-Woo, Lee, Sun-Young, Moon, DaeWon, Han, Seungwoo
Format:	Article
Language:	eng
Subjects:	Animals Arthritis Bone (subchondral) Bone Remodeling - physiology Bone remodelling Calcium - metabolism Calcium phosphates Cartilage (articular) Cartilage diseases Cartilage, Articular - metabolism Cell Differentiation Chondrocytes Chondrocytes - cytology Chondrocytes - metabolism Collagenase 3 Degeneration Disease Models, Animal Endocytosis Environmental changes Extracellular signal-regulated kinase Kinases Male Matrix Metalloproteinase 13 - metabolism Matrix Metalloproteinase 3 - metabolism Mice Mice, Inbred C57BL Mitogen-Activated Protein Kinase 1 - metabolism Mitogen-Activated Protein Kinase 3 - metabolism NF-kappa B - metabolism NF-κB protein Osteoarthritis Osteoarthritis - metabolism Osteoarthritis - pathology Osteoclasts Phosphates - metabolism Signal Transduction Stat3 protein STAT3 Transcription Factor - metabolism Transcription
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Summary:	An activation of osteoclasts and subchondral bone remodeling is a major histologic feature of early-stage osteoarthritis (OA), which can be accompanied by an increase of calcium (Ca) and phosphate (Pi) level in the subchondral milieu. Considering articular cartilage gets most of nutrition from subchondral bone by diffusion, these micro-environmental changes in subchondral bone can affect the physiology of articular chondrocytes. Here, we have shown that Ca is increased and co-localized with Pi in articular cartilage of early-stage OA. The Ca-Pi complex increased the production of MMP-3 and MMP-13 in the hypertrophic chondrocytes, which was dependent on nuclear factor-kappa B (NF-kB), p38 and extracellular signal-regulated kinase (Erk) 1/2 mitogen-activated protein (MAP) kinase and Signal transducer and activator of transcription 3 (STAT3) signaling. The Ca-Pi complexes increased the expression of endocytosis markers, and the inhibition of the formation of the Ca-Pi complex ameliorated the Ca-Pi complex-mediated increases of MMPs expression in hypertrophic chondrocytes. Our data provide insight regarding the Ca-Pi complex as a potential catabolic mediator in the subchondral milieu and support the pathogenic role of subchondral bone in the early stages of cartilage degeneration.
ISSN:	2045-2322 2045-2322