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Increased subchondral bone angiogenesis with blood vessels breaching the tidemark into the avascular cartilage is a diagnostic feature of human osteoarthritis. However, the mechanisms that initiate subchondral bone angiogenesis remain unclear. We show that abnormally increased platelet-derived growth factor-BB (PDGF-BB) secretion by mononuclear preosteoclasts induces subchondral bone angiogenesis, contributing to osteoarthritis development. In mice after destabilization of the medial meniscus (DMM), aberrant joint subchondral bone angiogenesis developed during an early stage of osteoarthritis, before articular cartilage damage occurred. Mononuclear preosteoclasts in subchondral bone secrete excessive amounts of PDGF-BB, which activates platelet-derived growth factor receptor β (PDGFRβ) signaling in pericytes for neo-vessel formation. Selective knockout of PDGF-BB in preosteoclasts attenuates subchondral bone angiogenesis and abrogates joint degeneration and subchondral innervation induced by DMM. Transgenic mice that express PDGF-BB in preosteoclasts recapitulate pathological subchondral bone angiogenesis and develop joint degeneration and subchondral innervation spontaneously. Our study provides the first evidence that PDGF-BB derived from preosteoclasts is a key driver of pathological subchondral bone angiogenesis during osteoarthritis development and offers a new avenue for developing early treatments for this disease.
This article was published in the following journal.
Name: JCI insight
To describe the association of subchondral and systemic bone mineral density (BMD) with knee and hip replacements (KR and HR, respectively) due to osteoarthritis.
Osteoporotic osteoarthritis (OPOA) is a common bone disease mostly in the elderly, but the relationship between Osteoporotic (OP) and osteoarthritis (OA) is complex. It has been shown that knee loadin...
TGF-β1/Smad3 pathway promotes the pathological progression of subchondral bone in osteoarthritis (OA). The aim of this study was to determine the effect of low intensity pulsed ultrasound (LIPUS) on ...
Subchondral bone plays an important role in the pathological mechanisms of knee osteoarthritis (OA). High-resolution peripheral quantitative computed tomography (HR-pQCT) is an imaging modality allowi...
Prenatal dexamethasone exposure (PDE) induces developmental toxicities of multi-organs and susceptibility to multi-diseases in offspring. However, the effects of PDE on osteoarthritis susceptibility i...
Predictive factors of osteoarthritis progression are not yet well understood. However, a growing role attaches importance to the subchondral bone. The aim of the present project is to dete...
Patients with osteoarthritis of the knee undergo visible joint changes in radiology and Magnetic resonance imaging (MRI) tests, but also clinically and histologically. The area of greatest...
Osteoarthritis is a very common pathology, especially in an aging population, and a source of disability. Based on standard radiography, the diagnosis is performed late based on the loss o...
Recently there has been a growing interest in the role of subchondral bone in knee arthritis, both in its etiology and evolution and in its clinical significance. It has now been widely de...
The aim of this study was to assess a novel approach to treating severe knee osteoarthritis by targeting synovialmembrane, superficial articular cartilage, synovial fluid, and subchondral ...
A degenerative joint disease involving the SPINE. It is characterized by progressive deterioration of the spinal articular cartilage (CARTILAGE, ARTICULAR), usually with hardening of the subchondral bone and outgrowth of bone spurs (OSTEOPHYTE).
Surgical techniques used to correct or augment healing of chondral defects in the joints (CARTILAGE, ARTICULAR). These include abrasion, drilling, and microfracture of the subchondral bone to enhance chondral resurfacing via autografts, allografts, or cell transplantation.
A PDGF receptor that binds specifically to both PDGF-A chains and PDGF-B chains. It contains a protein-tyrosine kinase activity that is involved in SIGNAL TRANSDUCTION.
A PDGF receptor that binds specifically to the PDGF-B chain. It contains a protein-tyrosine kinase activity that is involved in SIGNAL TRANSDUCTION.
Specific receptors on cell membranes that react with PLATELET-DERIVED GROWTH FACTOR, its analogs, or antagonists. The alpha PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR ALPHA) and the beta PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR BETA) are the two principle types of PDGF receptors. Activation of the protein-tyrosine kinase activity of the receptors occurs by ligand-induced dimerization or heterodimerization of PDGF receptor types.
Osteoporosis is a disease in which the bones become extremely porous, are subject to fracture, and heal slowly, occurring especially in women following menopause and often leading to curvature of the spine from vertebral collapse. Follow and track&n...
Arthritis is by definition the inflammation of one or more joints, characterized by swelling, pain, warmth, redness and diminished range of joint movement (Oxford Medical Dictionary). There are many different types; Noninflammatory; Osteoarthritis, N...