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Synovial chondromatosis: Novel advances in understanding the pathogenesis and in diagnostic strategies (Review)

  • Authors:
    • Xingzheng Deng
    • Shizhang Liu
    • Huitong Liu
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    Affiliations: Department of Orthopedics, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China
    Copyright: © Deng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 33
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    Published online on: November 10, 2025
       https://doi.org/10.3892/mmr.2025.13743
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Abstract

Synovial chondromatosis (SC) is a relatively rare benign synovial disorder characterized by the abnormal chondroid metaplasia of synovial cells, leading to the formation of multiple cartilage nodules that affect both intra‑articular and extra‑articular synovial tissues. Although the pathogenesis of SC remains incompletely understood, various signaling pathways, the inflammatory microenvironment and mechanical stress carry out key roles in the progression of the disease. Given the advancements in imaging techniques and the pathological mechanisms at play, early diagnosis and lesion evaluation of SC have markedly improved. In terms of treatment, both arthroscopic and open surgeries remain the primary approaches, with total synovectomy is the preferred method given the reduction in recurrence rates. The exploration of biologic agents offers novel possibilities for non‑surgical management. Despite the generally benign nature of SC, recurrent occurrences and the potential for malignant transformation require careful monitoring. Future research should focus on molecular‑targeted therapies, early detection and precision therapeutics to optimize clinical management and long‑term outcomes of patients with SC. The present review discusses the pathogenesis, diagnostic methods, treatment strategies and future research directions of SC, aiming to provide a comprehensive theoretical framework for its clinical management.
View Figures

Figure 1

The progression of synovial cartilage
nodule formation. As the nodules increase in size, certain areas
may calcify, ultimately developing into mature synovial
chondromatosis. In the later stages of the disease, normal joint
structure and function are progressively destroyed, leading to
joint instability and dysfunction, markedly impairing the mobility
of the patient (in this figure, black arrows identify core
structures such as ‘joint cavity’, ‘nodules’, ‘calcifications’ and
‘loose bodies’ at each stage; large blue arrows indicate the
sequential process of synovial cartilage nodule formation).

Figure 2

Schematic illustration of synoviocyte
chondrogenic metaplasia in SC. This figure illustrates the process
of chondroid metaplasia in synovial cells in SC. As the cells
proliferate and secrete cartilage matrix, the matrix accumulates
between the cells and synovial cells gradually differentiate into
chondrocytes, ultimately leading to chondrogenesis and
calcification. SC, synovial chondromatosis (in this figure, black
arrows identify core components such as synovial cells, cartilage
matrix and chondrocytes at each stage; large blue arrows indicate
the sequential process of synoviocyte chondrogenic metaplasia).

Figure 3

Schematic diagram of the key factors
affecting SC. SC, synovial chondromatosis.

Figure 4

Schematic diagram of the roles of
four major signaling pathways (Hedgehog, FGF, TGF-β and IL-6) in
the pathogenesis of SC. (A) Hedgehog pathway: The HH ligand binds
to the PTC1 receptor, relieving the inhibition of the SMO receptor,
which activates Gli proteins and causes them to dissociate from the
complex formed by COS2, FU and SUFU. This activation subsequently
upregulates the expression of genes such as Cyclin D1, Col2A1 and
Aggrecan. (B) FGF pathway: After the FGF ligand binds to the FGFR
receptor, it activates the IP3-DAG-PKC, MAPK/ERK and PI3K/Akt
signaling pathways, leading to the expression of genes including
calcium ions, Cyclin D1, Bcl-2 and c-Myc. (C) TGF-β pathway: The
TGF-β ligand binds to the TGF-βRII receptor, activating the
tyrosine phosphorylation of the TGF-βRI receptor, which in turn
activates the Smad2/3 signaling pathway. The activated Smad complex
then enters the nucleus, regulating genes associated with
chondrogenesis and cell proliferation, such as Col2A1, Aggrecan,
Sox9 and Cyclin D1. (D) IL-6 pathway: IL-6 binds to its receptor
IL-6R, activating the JAK/STAT signaling pathway, which promotes
the expression of Cyclin D1, c-Myc, Bcl-2 and VEGF. Ultimately, the
upregulation of these genes promotes cell proliferation, inhibits
apoptosis, accelerates synovial cell differentiation and
chondrogenesis, and thus facilitates the formation of SC. Bcl-2,
B-cell lymphoma 2; c-Myc, cellular Myc; Col2A1, collagen type IIα1;
DAG, diacylglycerol; FGFR, fibroblast growth factor receptor; FGF,
fibroblast growth factor; Gli, Glioma-associated oncogene homolog;
HH, Hedgehog; IL-6, interleukin 6; IL-6R, IL-6 receptor; IP3,
inositol 1,4,5-trisphosphate; IP3R, inositol 1,4,5-trisphosphate
receptor; JAK/STAT, Janus kinase/signal transducer and activator of
transcription; MAPK/ERK, mitogen-activated protein
kinase/extracellular signal-regulated kinase; MMPs, matrix
metalloproteinases; mTOR, mechanistic target of rapamycin;
PI3K/Akt, phosphoinositide 3-kinase/protein kinase B; PIP2,
phosphatidylinositol 4,5-bisphosphate; PKC, protein kinase C; PTC1,
Patched 1; SC, synovial chondromatosis; Smad2/3/4, Smad family
proteins 2/3/4; Sox9, SRY-box 9; SMO, Smoothened; SUFU, suppressor
of FU; TGF-βRI, transforming growth factor-β receptor I; VEGF,
vascular endothelial growth factor; COS2, Costal 2; FU, Fused.

Figure 5

Schematic diagram of the impact of
signaling pathway regulatory products, inflammatory
microenvironment and mechanical stress on the pathogenesis of SC.
i) Impact of factors: Bcl-2, Cyclin D1, GLI1, P21 and c-Myc
primarily promote the growth and proliferation of synovial cells
and inhibit apoptosis. Aggrecan, calcium ions, Col2A1 and MMPs
promote the synthesis of cartilage matrix and cartilage repair.
VEGF-A promotes cell proliferation and angiogenesis through the
MAPK/ERK and PI3K/Akt pathways. ii) Impact of an inflammatory
microenvironment: CD+macrophages and
HLA-DR+cells secrete inflammatory cytokines, such as
IL-1β, TNF-α, IL-6, IL-17 and IFN-γ. These cytokines enhance
synovial inflammation, strengthen immune responses and accelerate
synovial cell proliferation. iii) Impact of mechanical stress:
Mechanical stress upregulates the expression of TNF-α, IL-1β, CD105
and CD90, promoting synovial cell proliferation, cartilage matrix
synthesis, chondrogenesis and calcification, further driving the
formation of chondromas. iv) Impact of other factors: Other
factors, such as C-erbB-2, promote the proliferation of synovial
cells through the MAPK/ERK and PI3K/Akt pathways and inhibit
apoptosis. The abnormal proliferation of CD34+progenitor
cells provides a source of cells for chondrogenesis and
calcification. TWIST1, TGF-β1 and harmine act synergistically to
further promote the formation and progression of SC. These factors
and mechanisms interact through different signaling pathways,
collectively driving the occurrence and development of SC. Bcl-2,
B-cell lymphoma 2; BMP-2/4, bone morphogenetic protein 2/4; c-Myc,
cellular Myc; Col2A1, collagen type IIα1; erbB-2, receptor
tyrosine-protein kinase ErbB-2; Gli1, glioma-associated oncogene
homolog 1; HLA-DR+, human leukocyte antigen-DR;
IL-6/17/1β, interleukin 6/17/1β; MAPK/ERK, mitogen-activated
protein kinase/extracellular signal-regulated kinase; MMPs, matrix
metalloproteinases; PI3K/Akt, phosphoinositide 3-kinase/protein
kinase B; SC, synovial chondromatosis; Smad, Smad family protein;
Sox9, SRY-box 9; TGF-βRI, transforming growth factor-β receptor I;
TNF-α/γ, tumor necrosis factor-α/γ; TWIST1, twist family BHLH
transcription factor 1; VEGF, vascular endothelial growth
factor.
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Copy and paste a formatted citation
Spandidos Publications style
Deng X, Liu S and Liu H: Synovial chondromatosis: Novel advances in understanding the pathogenesis and in diagnostic strategies (Review). Mol Med Rep 33: 33, 2026.
APA
Deng, X., Liu, S., & Liu, H. (2026). Synovial chondromatosis: Novel advances in understanding the pathogenesis and in diagnostic strategies (Review). Molecular Medicine Reports, 33, 33. https://doi.org/10.3892/mmr.2025.13743
MLA
Deng, X., Liu, S., Liu, H."Synovial chondromatosis: Novel advances in understanding the pathogenesis and in diagnostic strategies (Review)". Molecular Medicine Reports 33.1 (2026): 33.
Chicago
Deng, X., Liu, S., Liu, H."Synovial chondromatosis: Novel advances in understanding the pathogenesis and in diagnostic strategies (Review)". Molecular Medicine Reports 33, no. 1 (2026): 33. https://doi.org/10.3892/mmr.2025.13743
Copy and paste a formatted citation
x
Spandidos Publications style
Deng X, Liu S and Liu H: Synovial chondromatosis: Novel advances in understanding the pathogenesis and in diagnostic strategies (Review). Mol Med Rep 33: 33, 2026.
APA
Deng, X., Liu, S., & Liu, H. (2026). Synovial chondromatosis: Novel advances in understanding the pathogenesis and in diagnostic strategies (Review). Molecular Medicine Reports, 33, 33. https://doi.org/10.3892/mmr.2025.13743
MLA
Deng, X., Liu, S., Liu, H."Synovial chondromatosis: Novel advances in understanding the pathogenesis and in diagnostic strategies (Review)". Molecular Medicine Reports 33.1 (2026): 33.
Chicago
Deng, X., Liu, S., Liu, H."Synovial chondromatosis: Novel advances in understanding the pathogenesis and in diagnostic strategies (Review)". Molecular Medicine Reports 33, no. 1 (2026): 33. https://doi.org/10.3892/mmr.2025.13743
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