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Calcium phosphate crystals raise MMP13 in human cartilage cells through a calcium signal

MMP13 biologyHuman cells2019

This 2019 study treated human cartilage cells with basic calcium phosphate crystals, which are often found in osteoarthritic joints. The cells made more MMP13, IL-6 and type X collagen and less SOX9. The crystals released calcium inside the cells and switched on the enzyme CaMK2, and blocking CaMK2 reduced every one of those changes.

Evidence typeHuman cells
Who or what was studiedPrimary chondrocytes from macroscopically normal human cartilage (number of donors not given in the abstract)
Dose and durationBCP crystals at 50 µg/mL for up to 48 hours

What they did

Researchers isolated chondrocytes from human cartilage that looked normal and treated them with basic calcium phosphate (BCP) crystals, a mix of hydroxyapatite, octacalcium apatite and tricalcium phosphate, for up to 48 hours. They measured markers of a shift in cell type, tracked calcium inside the cells and the enzyme CaMK2, then blocked or knocked down CaMK2 to see whether the changes depended on it.

What they found

At 50 µg/mL, BCP crystals raised the expression of Indian hedgehog, MMP13, interleukin-6 and type X collagen, and lowered SOX9, compared with untreated cells. Type X collagen protein appeared in the treated cells. Calcium inside the cells rose because the crystals released it from internal stores, and both phosphorylated and total CaMK2 went up. Inhibiting or knocking down CaMK2 reduced the crystal-driven changes in all five markers.

What it can't tell us

The work was done on isolated cells over at most 48 hours, at one main crystal concentration. The abstract does not say how many donors were used. It cannot tell us how often such crystals form in joints, or whether the same calcium pathway matters inside living cartilage.

Why it matters

Crystals are one of the physical triggers that can switch MMP13 on in cartilage cells. This paper traces the route, from crystal to calcium release to CaMK2 to MMP13, and shows the effect depends on that route. The authors suggest crystals in joints may add to cartilage breakdown.

The paper

  1. Rong J, Pool B, Zhu M et al. Basic Calcium Phosphate Crystals Induce Osteoarthritis-Associated Changes in Phenotype Markers in Primary Human Chondrocytes by a Calcium/Calmodulin Kinase 2-Dependent Mechanism. Calcif Tissue Int 2019.

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Last reviewed 3 November 2026Every study cited here is indexed on PubMed. How we read the evidence