Structural changes in the collagen network of joint tissues in late stages of murine OA

Natalie K. Yoshioka, Gregory M. Young, Deepak Kumar Khajuria, Vengadeshprabhu Karuppagounder, William J. Pinamont, Julie C. Fanburg-Smith, Thomas Abraham, Reyad A. Elbarbary, Fadia Kamal

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Osteoarthritis (OA) is the most prevalent degenerative joint disease, resulting in joint pain, impaired movement, and structural changes. As the ability of joint tissue to resist stress is mainly imparted by fibrillar collagens in the extracellular matrix, changes in the composition and structure of collagen fibers contribute to the pathological remodeling observed in OA joints that includes cartilage degeneration, subchondral bone (SCB) sclerosis, and meniscal damage. Using the established OA model of destabilization of the medial meniscus (DMM) in C57BL/6J mice, we performed a comprehensive analysis of the content and structure of collagen fibers in the articular cartilage, subchondral bone, and menisci using complementary techniques, which included second harmonic generation microscopy and immunofluorescence staining. We found that regions exposed to increased mechanical stress in OA mice, typically closest to the site of injury, had increased collagen fiber thickness, dysregulated fiber formation, and tissue specific changes in collagen I and II (Col I and Col II) expression. In cartilage, OA was associated with decreased Col II expression in all regions, and increased Col I expression in the anterior and posterior regions. Col I fiber thickness was increased in all regions with disorganization in the center region. In the superficial SCB, all regions exhibited increased Col I expression and fiber thickness in OA mice; no changes were detected in the deeper regions of the subchondral bone except for increased Col I fiber thickness. In the menisci, OA led to increased Col I and Col II expression in the vascular and avascular regions of the anterior meniscus with increased Col I fiber thickness in these regions. Similar changes were observed only in the vascular region of the posterior meniscus. Our findings provide, for the first time, comprehensive insights into the microarchitectural changes of extracellular matrix in OA and serve as guidelines for studies investigating therapies that target collagenous changes as means to impede the progression of osteoarthritis.

Original languageEnglish
Article number9159
JournalScientific Reports
Issue number1
StatePublished - Dec 2022
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by NIH NIAMS R01 AR071968 (to F.K.), ANRF Arthritis Research Grant (to F.K.), The Barsumian Fund (to F.K.), NIH NIDDK R01 DK121327 (to R.A.E.). We acknowledge the Molecular and Histopathology Core for support with sample processing, and the Microscopy Imaging Core for the use of the Nikon A1 MP+ Multi-Photon Upright Microscope System and SHG analysis equipment.

Publisher Copyright:
© 2022, The Author(s).


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