title: Chondropenia: current concept review.
abstract: The term "chondropenia" indicates the early stage of degenerative cartilage disease, and it has been identified by carefully monitoring early-stage osteoarthritis (OA). Not only is it the loss of articular cartilage volume, but it is also a rearrangement of biomechanical, ultrastructural, biochemical and molecular properties typical of healthy cartilage tissue. Diagnosing OA at an early stage or an advanced stage is valuable in terms of clinical and therapeutic outcome. In fact degenerative phenomena are supported by a complex biochemical cascade which unbalances the extracellular matrix homeostasis, closely regulated by chondrocytes. In the first stage an intense inflammatory reaction is triggered: pro-catabolic cytokines such as IL-1β and TNF-α triggering matrix metalloproteases and aggrecanase (ADAMT-4 and 5), responsible for the early loss of ultrastructural components, such as type II collagen and aggrecan. In addition nitric oxide and reactive oxygen species modulate the physiopathology of the condral matrix inducing apoptosis of chondrocytes through a mitochondria-dependent pathway. In addition, "Lonely Death": chondrocytes, are confined within a dense, avascular extracellular matrix capsule, and can trigger a genetically induced apoptosis and necrosis. The degenerative process starts from a central point and then spreads in a centrifugal manner in depth and in adjacent areas, eventually covering the whole joint; chondropenia represents a journey from the first clinically detectable time-point until it can be characterized as frank osteoarthritis. Currently, there are no instruments sensitive enough which allow a timely diagnosis of chondropenia. Innovative magnetic resonance imaging techniques, such as T2 mapping, can be effective and a sensitive diagnostic instrument for quantifying cartilage volume and proteoglycan content. However, avant-garde biophysical techniques, such as mechanical indenters, ultrasound and biochemical markers (uCTX-II), are rational and scientific tools applicable to the clinical and therapeutic management of early degenerative cartilage disease. The objective of this review on chondropenia is to present a state of the art and innovative concepts.
authors.affiliation: Institute of Orthopedic and Traumatology, Catholic University, 'A. Gemelli' Hospital, Largo F. Vito1, 00168, Rome, Italy. andrea.speziali@gmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Speziali
authors.affiliation: Institute of Orthopedic and Traumatology, Catholic University, 'A. Gemelli' Hospital, Largo F. Vito1, 00168, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Delcogliano
authors.affiliation: Institute of Orthopedic and Traumatology, Catholic University, 'A. Gemelli' Hospital, Largo F. Vito1, 00168, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Tei
authors.affiliation: Institute of Orthopedic and Traumatology, Catholic University, 'A. Gemelli' Hospital, Largo F. Vito1, 00168, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Placella
authors.affiliation: Institute of Orthopedic and Traumatology, Catholic University, 'A. Gemelli' Hospital, Largo F. Vito1, 00168, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Chillemi
authors.affiliation: Translational Research Institute for Musculoskeletal System 'Nicola Cerulli', LPMRI, Arezzo, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Tiribuzi
authors.affiliation: Institute of Orthopedic and Traumatology, Catholic University, 'A. Gemelli' Hospital, Largo F. Vito1, 00168, Rome, Italy. g_cerulli@tin.it.|Translational Research Institute for Musculoskeletal System 'Nicola Cerulli', LPMRI, Arezzo, Italy. g_cerulli@tin.it.|, G.B. Pontani 9, 06128, Perugia, Italy. g_cerulli@tin.it.
authors.forename: G
authors.initials: G
authors.lastname: Cerulli
mesh_terms: D015415:Biomarkers / Q000097:blood; D002357:Cartilage Diseases / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology*; D002358:Cartilage, Articular / Q000473:pathology*; D019902:Chondrocytes / Q000473:pathology*; D016207:Cytokines / Q000276:immunology*; D018450:Disease Progression; D010450:Endopeptidases / Q000276:immunology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D020782:Matrix Metalloproteinases / Q000276:immunology; D010003:Osteoarthritis / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D011237:Predictive Value of Tests; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D015415:Biomarkers; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D010450:Endopeptidases; D020782:Matrix Metalloproteinases; C083641:aggrecanase
keywords: Cartilage degeneration; Chondropenia; Early osteoarthritis; Matrix metalloproteases