Chinese scholars have made progress in osteoarthritis research

Figure The process and mechanism of top-down and bottom-up bidirectional cartilage calcification in the progression of human knee OA

With the support of the National Natural Science Foundation of China (grant number: T2121004, 31830029, 82002271, 81902187), Professor Ouyang Hongwei's research group of Zhejiang University revealed for the first time the pathological mechanism of top-down and bottom-up bidirectional calcified articular cartilage layer in the development of osteoarthritis (OA) from the multidisciplinary perspectives of material molecular assembly, microstructure and micromechanics.
Top-down calcification refers to the gradual calcification from the joint cavity to the articular surface at the articular surface, and bottom-up calcification refers to the sandwich feature
of "bone-cartilage-calcified cartilage" that occurs at the osteochondral junction by jumping calcification of the subchondral bone to the articular cartilage layer 。 The results were published in the Annals of Rheumatic Diseases under the title
"Stage-specific and location-specific cartilage calcification in osteoarthritis development.
" 。 The link to the paper is: https://ard.
bmj.
com/content/early/2022/10/19/ard-2022-222944
.

Osteoarthritis (OA) is the most prevalent knee disease with an extremely high
rate of disability.
The pathological calcification of cartilage has greatly promoted the progress of OA, but little is currently known about the pathological calcification process of cartilage during the development of OA, including the nucleation of early minerals, the growth and maturation of crystals, and how it promotes the progress of OA
.
There are no drugs or treatment options that can prevent crystal precipitation in OA cartilage tissue or dissolve crystals
formed in cartilage.
Therefore, exploring the pathological calcification process and mechanism of cartilage can provide potential targets and directions
for the pathological calcification treatment of OA.

From the perspective of material science, Professor Ouyang Hongwei's team used a variety of high-resolution material characterization methods to find that the pathological calcification of cartilage occurred in the very early stage of OA, and presented the pathological calcification process of top-down cartilage from the surface of cartilage and the bottom-up two-way calcification process of calcified cartilage (Figure).

The top-down calcification that occurs in the early stage of OA starts from the cartilage surface damage and fibrotic area, and forms spherical nanoparticles.
In late OA cartilage, minerals are fibers and dense assembly structures, and further invade deep cartilage
.
Early bottom-up calcification of OA begins with the characteristic sandwich calcification structure that appears at the calcified cartilage, and acids and mast chondrocytes near the tidal line promote the formation
of this characteristic structure.
With the development of OA, the sandwich calcified structures at the calcified cartilage fuse, and the calcified cartilage area thickens, further invading
the upper layer of cartilage.
Compared with normal samples, the crystalline crystallinity of calcified cartilage in the early stage of OA increased and the mechanical properties were improved, while the calcified cartilage in the late stage of OA showed a completely opposite trend
.
This difference may be attributed to different crystal nucleation patterns regulated by mast chondrocytes at calcified cartilage, with stromal vesicle nucleation in the early OA and carbonate nucleation
in the late OA.

Based on the mechanism of bidirectional calcified cartilage during the development of OA, targeted therapies
to prevent pathological calcification can be developed in the future.
For top-down calcification of the joint surface, it can be developed to prevent early formation and growth
of crystals by inhibiting the transdifferentiation of chondrocytes and reducing the concentration of^Ca2+ and PO4^3- ions in synovial fluid.
For bottom-up cartilage calcification at calcified cartilage, therapeutic strategies
that regulate cellular metabolic activity need to be designed.

This study improves the current understanding of the pathological development mechanism of OA from the perspective of material science, explores the pathological characteristics of position- and stage-specific bidirectional cartilage calcification in the development of human knee OA, discusses its contribution to the development of OA, and provides new directions
for potential therapeutic targeting strategies.