Personal non-commercial use only

ABSTRACT. Objective. The morphology of articular cartilage (AC) enables painless movement. Aging and mechanical loading are believed to influence development of osteoarthritis (OA), yet the connection remains unclear. Methods. This narrative review describes the current knowledge regarding this area, with the literature search made on PubMed using appropriate keywords regarding AC, age, and mechanical loading. Results. Following skeletal maturation, chondrocyte numbers decline while increasing senescence occurs. Lower cartilage turnover causes diminished maintenance capacity, which produces accumulation of fibrillar crosslinks by advanced glycation end products, resulting in increased stiffness and thereby destruction susceptibility. Articular cartilage (AC) covers bone surfaces and allows for almost friction-free movement. Unfortunately, AC is susceptible to acute injury and degenerative conditions, e.g., osteoarthritis (OA), and because cartilage has very poor healing potential, OA is a considerable medical challenge. OA is no longer solely seen as 1 single disease, instead 5 OA phenotypes have been suggested, i.e., genetic, metabolic, pain, age, and structural/post-traumatic 1 . Our narrative review is meant as a covering overview of the main OA phenotypes (related to aging and mechanical loading), and is aimed to include studies of molecular, biochemical, physiological, and clinical designs. To clarify these OA phenotypes, basic information about AC morphology and key components is provided. This is followed by a review of the effect of age and mechanical influence on the morphology, along with the underlying cell signaling, because, as demonstrated, OA is not merely a mechanical/physical "wear and tear" disease. The literature search was performed on PubMed using appropriate keywords regarding exercise/mechanical load, articular cartilage, metabolism/turnover, OA, extracellular matrix, and cell signaling/transduction. Morphology AC consists of the chondrocyte surrounded by an extracellular matrix (ECM), subdivided into areas in a pericellular matrix (PCM) immediately adjacent to the cell, a territorial matrix farther away, and an interterritorial matrix 2 . ECM contains a fibrillar network of both collagens and noncollagenous matrix components embedded in a viscous gel-like ground/basic substance. The fibers are oriented differently and divide the uncalcified AC into 3 zones: superficial zone (SZ) with parallel fiber orientation, intermediate zone (IZ) with random, and finally deep zone (DZ) with vertical orientation. A tidemark represents the DZ transition into the mineralized/calcified fourth zone followed by the subchondral bone below 3 . The ground/basic substance contains the extra

Use of Cis-[18F]Fluoro-Proline for Assessment of Exercise-Related Collagen Synthesis in Musculoskeletal Connective Tissue

Protein turnover in collagen rich tissue is influenced by exercise, but can only with difficulty be studied in vivo due to use of invasive procedure. The present study was done to investigate the possibility of applying the PET-tracer, cis-[18F]fluoro-proline (cis-Fpro), for non-invasive assessment of collagen synthesis in rat musculoskeletal tissues at rest and following short-term (3 days) treadmill running. Musculoskeletal collagen synthesis was studied in rats at rest and 24 h post-exercise. At each session, rats were PET scanned at two time points following injection of cis-FPro: (60 and 240 min p.i). SUV were calculated for Achilles tendon, calf muscle and tibial bone. The PET-derived results were compared to mRNA expression of collagen type I and III. Tibial bone had the highest SUV that increased significantly (p<0.001) from the early (60 min) to the late (240 min) PET scan, while SUV in tendon and muscle decreased (p<0.001). Exercise had no influence on SUV, which was contradicted by an increased gene expression of collagen type I and III in muscle and tendon. The clearly, visible uptake of cis-Fpro in the collagen-rich musculoskeletal tissues is promising for multi-tissue studies in vivo. The tissue-specific differences with the highest basal uptake in bone are in accordance with earlier studies relying on tissue incorporation of isotopic-labelled proline. A possible explanation of the failure to demonstrate enhanced collagen synthesis following exercise, despite augmented collagen type I and III transcription, is that SUV calculations are not sensitive enough to detect minor changes in collagen synthesis. Further studies including kinetic compartment modeling must be performed to establish whether cis-Fpro can be used for non-invasive in-vivo assessment of exercise-induced changes in musculoskeletal collagen synthesis

Lack of tissue renewal in human adult Achilles tendon is revealed by nuclear bomb (14)C

Tendons are often injured and heal poorly. Whether this is caused by a slow tissue turnover is unknown, since existing data provide diverging estimates of tendon protein half-life that range from 2 mo to 200 yr. With the purpose of determining life-long turnover of human tendon tissue, we used the (14)C bomb-pulse method. This method takes advantage of the dramatic increase in atmospheric levels of (14)C, produced by nuclear bomb tests in 1955–1963, which is reflected in all living organisms. Levels of (14)C were measured in 28 forensic samples of Achilles tendon core and 4 skeletal muscle samples (donor birth years 1945–1983) with accelerator mass spectrometry (AMS) and compared to known atmospheric levels to estimate tissue turnover. We found that Achilles tendon tissue retained levels of (14)C corresponding to atmospheric levels several decades before tissue sampling, demonstrating a very limited tissue turnover. The tendon concentrations of (14)C approximately reflected the atmospheric levels present during the first 17 yr of life, indicating that the tendon core is formed during height growth and is essentially not renewed thereafter. In contrast, (14)C levels in muscle indicated continuous turnover. Our observation provides a fundamental premise for understanding tendon function and pathology, and likely explains the poor regenerative capacity of tendon tissue.—Heinemeier, K. M., Schjerling, P., Heinemeier, J., Magnusson, S. P., Kjaer, M. Lack of tissue renewal in human adult Achilles tendon is revealed by nuclear bomb (14)C

:4; Personal non-commercial use only

ABSTRACT. Objective. The morphology of articular cartilage (AC) enables painless movement. Aging and mechanical loading are believed to influence development of osteoarthritis (OA), yet the connection remains unclear. Methods. This narrative review describes the current knowledge regarding this area, with the literature search made on PubMed using appropriate keywords regarding AC, age, and mechanical loading. Results. Following skeletal maturation, chondrocyte numbers decline while increasing senescence occurs. Lower cartilage turnover causes diminished maintenance capacity, which produces accumulation of fibrillar crosslinks by advanced glycation end products, resulting in increased stiffness and thereby destruction susceptibility. Articular cartilage (AC) covers bone surfaces and allows for almost friction-free movement. Unfortunately, AC is susceptible to acute injury and degenerative conditions, e.g., osteoarthritis (OA), and because cartilage has very poor healing potential, OA is a considerable medical challenge. OA is no longer solely seen as 1 single disease, instead 5 OA phenotypes have been suggested, i.e., genetic, metabolic, pain, age, and structural/post-traumatic 1 . Our narrative review is meant as a covering overview of the main OA phenotypes (related to aging and mechanical loading), and is aimed to include studies of molecular, biochemical, physiological, and clinical designs. To clarify these OA phenotypes, basic information about AC morphology and key components is provided. This is followed by a review of the effect of age and mechanical influence on the morphology, along with the underlying cell signaling, because, as demonstrated, OA is not merely a mechanical/physical &quot;wear and tear&quot; disease. The literature search was performed on PubMed using appropriate keywords regarding exercise/mechanical load, articular cartilage, metabolism/turnover, OA, extracellular matrix, and cell signaling/transduction. Morphology AC consists of the chondrocyte surrounded by an extracellular matrix (ECM), subdivided into areas in a pericellular matrix (PCM) immediately adjacent to the cell, a territorial matrix farther away, and an interterritorial matrix 2 . ECM contains a fibrillar network of both collagens and noncollagenous matrix components embedded in a viscous gel-like ground/basic substance. The fibers are oriented differently and divide the uncalcified AC into 3 zones: superficial zone (SZ) with parallel fiber orientation, intermediate zone (IZ) with random, and finally deep zone (DZ) with vertical orientation. A tidemark represents the DZ transition into the mineralized/calcified fourth zone followed by the subchondral bone below 3 . The ground/basic substance contains the extra