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

Abstract

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.

SDF-1α promotes subchondral bone sclerosis and aggravates osteoarthritis by regulating the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells

“…Because the tissue damage caused by DMM is insignificant, the disease progresses slowly; mild changes were observed 2 weeks after surgery, and marked changes were observed at 8 weeks, mainly in the tibial plateau [ 16 ]. These changes are similar to the pathological changes observed in humans; thus, this animal model of the disease has been used to study its pathology [ 17 ]. Therefore, in this study, an OA model was constructed by DMM.…”

Regulation of pain neurotransmitters and chondrocytes metabolism mediated by voltage-gated ion channels: A narrative review

“…The pathological basis of OA is related to cartilage degeneration, accompanied by a decrease in the chondrocytes' anabolism and an increase in the chondrocytes' catabolism [ 101 ]. Knee peripheral receptors transmit nociceptive signals to the DRG, releasing pain-causing neurotransmitters.…”

Cannabidiol and Cannabigerol, Nonpsychotropic Cannabinoids, as Analgesics that Effectively Manage Bone Fracture Pain and Promote Healing in Mice

“…IF staining was performed as we previously detailed (2,26,(38)(39)(40) (all antibodies are listed in Table S1). Mounting and nuclear staining were performed using ProLong™ Gold antifade reagent with DAPI (Invitrogen).…”