Collagens are the most abundant components of the extracellular matrix and many types of soft tissues. Elastin is another major component of certain soft tissues, such as arterial walls and ...ligaments. Many other molecules, though lower in quantity, function as essential components of the extracellular matrix in soft tissues. Some of these are reviewed in this chapter. Besides their basic structure, biochemistry and physiology, their roles in disorders of soft tissues are discussed only briefly as most chapters in this volume deal with relevant individual compounds. Fibronectin with its muldomain structure plays a role of "master organizer" in matrix assembly as it forms a bridge between cell surface receptors, e.g., integrins, and compounds such collagen, proteoglycans and other focal adhesion molecules. It also plays an essential role in the assembly of fibrillin-1 into a structured network. Laminins contribute to the structure of the extracellular matrix (ECM) and modulate cellular functions such as adhesion, differentiation, migration, stability of phenotype, and resistance towards apoptosis. Though the primary role of fibrinogen is in clot formation, after conversion to fibrin by thrombin, it also binds to a variety of compounds, particularly to various growth factors, and as such fibrinogen is a player in cardiovascular and extracellular matrix physiology. Elastin, an insoluble polymer of the monomeric soluble precursor tropoelastin, is the main component of elastic fibers in matrix tissue where it provides elastic recoil and resilience to a variety of connective tissues, e.g., aorta and ligaments. Elastic fibers regulate activity of TGFβs through their association with fibrillin microfibrils. Elastin also plays a role in cell adhesion, cell migration, and has the ability to participate in cell signaling. Mutations in the elastin gene lead to cutis laxa. Fibrillins represent the predominant core of the microfibrils in elastic as well as non-elastic extracellular matrixes, and interact closely with tropoelastin and integrins. Not only do microfibrils provide structural integrity of specific organ systems, but they also provide a scaffold for elastogenesis in elastic tissues. Fibrillin is important for the assembly of elastin into elastic fibers. Mutations in the fibrillin-1 gene are closely associated with Marfan syndrome. Fibulins are tightly connected with basement membranes, elastic fibers and other components of extracellular matrix and participate in formation of elastic fibers. Tenascins are ECM polymorphic glycoproteins found in many connective tissues in the body. Their expression is regulated by mechanical stress both during development and in adulthood. Tenascins mediate both inflammatory and fibrotic processes to enable effective tissue repair and play roles in pathogenesis of Ehlers-Danlos, heart disease, and regeneration and recovery of musculo-tendinous tissue. One of the roles of thrombospondin 1 is activation of TGFβ. Increased expression of thrombospondin and TGFβ activity was observed in fibrotic skin disorders such as keloids and scleroderma. Cartilage oligomeric matrix protein (COMP) or thrombospondin-5 is primarily present in the cartilage. High levels of COMP are present in fibrotic scars and systemic sclerosis of the skin, and in tendon, especially with physical activity, loading and post-injury. It plays a role in vascular wall remodeling and has been found in atherosclerotic plaques as well.
The vascular endothelium is an important mediator of tissue vasodilatation, yet the role of the specific substances, nitric
oxide (NO) and prostaglandins (PG), in mediating the large increases in ...muscle perfusion during exercise in humans is unclear.
Quadriceps microvascular blood flow was quantified by near infrared spectroscopy and indocyanine green in six healthy humans
during dynamic knee extension exercise with and without combined pharmacological inhibition of NO synthase (NOS) and PG by
l -NAME and indomethacin, respectively. Microdialysis was applied to determine interstitial release of PG. Compared to control,
combined blockade resulted in a 5- to 10-fold lower muscle interstitial PG level. During control incremental knee extension
exercise, mean blood flow in the quadriceps muscles rose from 10 ± 0.8 ml (100 ml tissue) â1 min â1 at rest to 124 ± 19, 245 ± 24, 329 ± 24 and 312 ± 25 ml (100 ml tissue) â1 min â1 at 15, 30, 45 and 60 W, respectively. During inhibition of NOS and PG, blood flow was reduced to 8 ± 0.5 ml (100 ml tissue) â1 min â1 at rest, and 100 ± 13, 163 ± 21, 217 ± 23 and 256 ± 28 ml (100 ml tissue) â1 min â1 at 15, 30, 45 and 60 W, respectively ( P < 0.05 vs. control). In conclusion, combined inhibition of NOS and PG reduced muscle blood flow during dynamic exercise in humans. These
findings demonstrate an important synergistic role of NO and PG for skeletal muscle vasodilatation and hyperaemia during muscular
contraction.
The mitochondrial theory of aging was tested with optimised preparation techniques. Mitochondria were isolated from ∼90 mg quadriceps muscle from healthy humans at age 70+ and 20+. The content of ...mitochondrial protein was ∼10 mg g
−1 muscle and the yields were ∼40%. The mitochondrial integrity was high as judged from the respiratory control and P/O ratios. No general membrane alterations or changes in the cytochrome contents were observed. BSA decreased the non-phosphorylating rates of respiration equally in both age groups. Thirteen different enzyme activities were assayed and normalised to protein content and citrate synthase activity. Most of the critical levels for detection of declines were <10%. In the 70+ group, the activity for fatty acid oxidation was decreased by ∼20%. Two inherently low activities associated with oxidation of sarcoplasmic NADH were also decreased, probably related to the age change of fibre types. The remaining activities measured, e.g. those of pyruvate dehydrogenase, tricarboxylic acid cycle, respiratory chain, and ATP synthesis, were not observed to be lowered. Thus, the central bioenergetic systems appeared unaltered with age. The obvious discord with reported age declines of human skeletal muscle mitochondrial function is discussed. It is concluded that the present results are incompatible with the mitochondrial theory of aging.
Physical activity is known to increase type I collagen synthesis measured as the concentration of biomarkers in plasma. By
the use of microdialysis catheters with a very high molecular mass cut-off ...value (3000 kDa) we aimed to determine local type
I collagen synthesis and degradation in the peritendinous region by measuring interstitial concentrations of a collagen propeptide
(PICP; 100 kDa) and a collagen degradation product (ICTP; 9 kDa) as well as an inflammatory mediator (PGE 2 ).
Seven trained human runners were studied before and after (2 and 72 h) 3 h of running (36 km). Two microdialysis catheters
were placed in the peritendinous space ventral to the Achilles' tendon under ultrasound guidance and perfused with a Ringer-acetate
solution containing 3 H-labelled human type IV collagen and 15- 3 H(N)PGE 2 for in vivo recovery determination. Relative recovery was 37â59% (range of the s.e.m. values) for both radioactively labelled substances.
PICP concentration decreased in both interstitial peritendinous tissue and arterial blood immediately after exercise, but
rose 3-fold from basal 72 h after exercise in the peritendinous tissue (55 ± 10 μg l â1 , mean ± s.e.m. (rest) to 165 ± 40 μg l â1 (72 h), P < 0·05) and by 25% in circulating blood (160 ± 10 μg l â1 (rest) to 200 ± 12 μg l â1 (72 h), P < 0·05). ICTP concentration did not change in blood, but decreased transiently in tendon-related tissue during early recovery
after exercise only. PGE 2 concentration increased in blood during running, and returned to baseline in the recovery period, whereas interstitial PGE 2 concentration was elevated in the early recovery phase.
The findings of the present study indicate that acute exercise induces increased formation of type I collagen in peritendinous
tissue as determined with microdialysis and using dialysate fibre with a very high molecular mass cut-off. This suggests an
adaptation to acute physical loading also in non-bone-related collagen in humans.
Artiklen undersøger etableringen og reproduceringen af et moderne antropocentrisk kartografisk blik på verden. Et blik, der på meget væsentlig facon har bidraget til den anthropocene forandring af ...kloden, vi er begyndt at opfatte omfanget af de senere år. Artiklens hovedtese er den, at den moderne oplyste 1600-tals kartografi korrellerede med en samtidig udvikling af et mørkt imaginært rum afkoblet fra omverdenslig sansning, et rum som den barokke billedkunsts clairobscur udfoldede. Til sammen dannede dette kompleks en kartografisk-visuel motor, der bidrog til at gøre det moderne menneske delvist ude af stand til at opfatte den faktiske verden, det befandt sig i og påvirkede. Analysen er vidensarkæologisk. Fokus er derfor på at afdække, hvordan dette kompleks epistemisk set bliver muligt, hvordan det fungerer, og hvilken verden, det tillader det vestlige menneske at opfatte. Artiklen åbnes med et eksempel, der illustrerer denne motor i dens stadige funktion: Den franske oceanograf Jacques-Yves Cousteaus (1910-1997) tidlige undervandsoptagelser. Efter dette analyseres henholdsvis den meracorianske navigationsfaste kartografi og barokkens mørke billedrum.
The musculoskeletal system, crucial for movement and support, relies on the delicate balance of connective tissue homeostasis. Maintaining this equilibrium is essential for tissue health and ...function. There has been increasing evidence in the last decade that shows the circadian clock as a master regulator of extracellular matrix (ECM) homeostasis in several connective tissue clocks. Very recently, exercise has emerged as a significant entrainment factor for cartilage and intervertebral disc circadian rhythms. Understanding the implications of exercise on connective tissue peripheral clocks holds promise for enhancing tissue health and disease prevention. Exercise-induced factors such as heat, glucocorticoid release, mechanical loading, and inter-tissue crosstalk may play pivotal roles in entraining the circadian rhythm of connective tissues. This mini review underscores the importance of elucidating the mechanisms through which exercise influences circadian rhythms in connective tissues to optimize ECM homeostasis. Leveraging exercise as a modulator of circadian rhythms in connective tissues may offer novel therapeutic approaches to physical training for preventing musculoskeletal disorders and enhancing recovery.
ABSTRACT
Tendons are essential weight‐bearing structures that are often affected by tendinopathy, which leads to pain and impaired mobility. In healthy Achilles tendons, no significant renewal of the ...weight‐bearing collagen matrix seems to occur during adult life, but tendinopathy may lead to increased turnover. The carbon‐14 (14C) bomb pulse method was used to measure lifelong replacement rates of collagen in tendinopathic and healthy Achilles tendons (tendinopathic: n = 25, born 1937–1972. Healthy: n = 10, born 1929–1966). As expected, the healthy tendon collagen had not been replaced during adulthood, but in tendinopathic tendon, a substantial renewal had occurred. Modeling of the 14C data suggested that one half of the collagen in tendinopathic matrix had undergone continuous slow turnover for years before the presentation of symptoms. This finding allows for a new concept in tendon pathogenesis because it suggests that either the symptoms of tendinopathy represent a late phase of a very prolonged disease process, or an abnormally high collagen exchange could be a risk factor for tendon disorders rather than being a result of disease.—Heinemeier, K.M., Schjerling, P., Øhlenschlæger, T. F., Eismark, C., Olsen, J., Kjær, M. Carbon‐14 bomb pulse dating shows that tendinopathy is preceded by years of abnormally high collagen turnover. FASEB J. 32, 4763–4775 (2018). www.fasebj.org
Vækst præger kulturen på godt og ondt. Fra idéer om liv, skabelse, kultivering og fremskridt til uønsket, uforudsigelig, ukultiveret, epidemisk og monstrøs vækst. Fra skyskrabere til finansbobler til ...syntetisk kød til six packs til big data. Særligt i dag, hvor naturlige og kunstigt skabte vækstformer i stigende grad blander sig sammen, er spørgsmålet om hvad vækst gør – hvordan den virker, hvad det egentlig er, der fascinerer os ved den, og hvilke muligheder, begrænsninger og potentielle kriser, den fører med sig – blevet desto mere påtrængende. Periskop nr. 22 undersøger i et bredt kunsthistorisk og -teoretisk perspektiv, hvordan vækst er blevet tematiseret, udforsket og udfordret i kunsten.
The aim of the present study was to simultaneously examine skeletal muscle heat production and ATP turnover in humans during
dynamic exercise with marked differences in aerobic metabolism. This was ...done to test the hypothesis that efficiency is higher
in anaerobic than aerobic ATP resynthesis. Six healthy male subjects performed 90 s of low intensity knee-extensor exercise
with (OCC) and without thigh occlusion (CON-LI) as well as 90 s of high intensity exercise (CON-HI) that continued from the
CON-LI bout. Muscle heat production was determined by continuous measurements of muscle heat accumulation and heat release
to the blood. Muscle ATP production was quantified by repeated measurements of thigh oxygen uptake as well as blood and muscle
metabolite changes. All temperatures of the thigh were equalized to â37 °C prior to exercise by a water-perfused heating cuff.
Oxygen uptake accounted for 80 ± 2 and 59 ± 4 %, respectively, of the total ATP resynthesis in CON-LI and CON-HI, whereas
it was negligible in OCC. The rise in muscle temperature was lower ( P < 0.05) in OCC than CON-LI (0.32 ± 0.04 vs. 0.37 ± 0.03 °C). The mean rate of heat production was also lower ( P < 0.05) in OCC than CON-LI (36 ± 4 vs. 57 ± 4 J s â1 ). Mechanical efficiency was 52 ± 4 % after 15 s of OCC and remained constant, whereas it decreased ( P < 0.05) from 56 ± 5 to 32 ± 3 % during CON-LI. During CON-HI, mechanical efficiency transiently increased ( P < 0.05) to 47 ± 4 %, after which it decreased ( P < 0.05) to 36 ± 3 % at the end of CON-HI. Assuming a fully coupled mitochondrial respiration, the ATP turnover per unit of
work was calculated to be unaltered during OCC (â20 mmol ATP kJ â1 ), whereas it increased ( P < 0.05) from 21 ± 4 to 29 ± 3 mmol ATP kJ â1 during CON-LI and further ( P < 0.05) to 37 ± 3 mmol ATP kJ â1 during CON-HI. The present data confirm the hypothesis that heat loss is lower in anaerobic ATP resynthesis than in oxidative
phosphorylation and can in part explain the finding that efficiency declines markedly during dynamic exercise. In addition,
the rate of ATP turnover apparently increases during constant load low intensity exercise. Alternatively, mitochondrial efficiency
is lowered as exercise progresses, since ATP turnover was unaltered during the ischaemic exercise bout.
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