During the past 20 years, it has become generally accepted that the modulation of fibroblastic cells towards the myofibroblastic phenotype, with acquisition of specialized contractile features, is essential for connective-tissue remodelling during normal and pathological wound healing. Yet the myofibroblast still remains one of the most enigmatic of cells, not least owing to its transient appearance in association with connective-tissue injury and to the difficulties in establishing its role in the production of tissue contracture. It is clear that our understanding of the myofibroblast its origins, functions and molecular regulation will have a profound influence on the future effectiveness not only of tissue engineering but also of regenerative medicine generally.

/pdf/myofibroblasts-and-mechano-regulation-of-connective-tissue-nzvxuu0xbh.pdf

Myofibroblasts and mechano-regulation of connective tissue remodelling

Antimicrobial host defense peptides are produced by all complex organisms as well as some microbes and have diverse and complex antimicrobial activities. Collectively these peptides demonstrate a broad range of antiviral and antibacterial activities and modes of action, and it is important to distinguish between direct microbicidal and indirect activities against such pathogens. The structural requirements of peptides for antiviral and antibacterial activities are evaluated in light of the diverse set of primary and secondary structures described for host defense peptides. Peptides with antifungal and antiparasitic activities are discussed in less detail, although the broad-spectrum activities of such peptides indicate that they are important host defense molecules. Knowledge regarding the relationship between peptide structure and function as well as their mechanism of action is being applied in the design of antimicrobial peptide variants as potential novel therapeutic agents.

Peptide Antimicrobial Agents

Osteoarthritis (OA) is the most common form of arthritis and a major cause of pain and disability in older adults (1) Often OA is referred to as degenerative joint disease “(DJD)” This is a misnomer because OA is not simply a process of wear and tear but rather abnormal remodeling of joint tissues driven by a host of inflammatory mediators within the affected joint The most common risk factors for OA include age, gender, prior joint injury, obesity, genetic predisposition, and mechanical factors, including malalignment and abnormal joint shape (2, 3) Despite the multifactorial nature of OA, the pathological changes seen in osteoarthritic joints have common features that affect the entire joint structure resulting in pain, deformity and loss of function

The pathologic changes seen in OA joints (Figures 1 and ​and2)2) include degradation of the articular cartilage, thickening of the subchondral bone, osteophyte formation, variable degrees of synovial inflammation, degeneration of ligaments and, in the knee, the menisci, and hypertrophy of the joint capsule There can also be changes in periarticular muscles, nerves, bursa, and local fat pads that may contribute to OA or the symptoms of OA The findings of pathological changes in all of the joint tissues are the impetus for considering OA as a disease of the joint as an organ resulting in “joint failure” In this review, we will summarize the key features of OA in the various joint tissues affected and provide an overview of the basic mechanisms currently thought to contribute to the pathological changes seen in these tissues






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Figure 1


Sagittal inversion recovery (A–C) and coronal fast spin echo (D–F) images illustrating the magnetic resonance imaging findings of osteoarthritis (A) reactive synovitis (thick white arrow), (B) subchondral cyst formation (white arrow), (C) bone marrow edema (thin white arrows), (D) partial thickness cartilage wear (thick black arrow), (E–F) full thickness cartilage wear (thin black arrows), subchondral sclerosis (arrowhead) and marginal osteophyte formation (double arrow) Image courtesy of Drs Hollis Potter and Catherine Hayter, Hospital for Special Surgery, New York, NY

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.34453

Osteoarthritis: A Disease of the Joint as an Organ

Application of chitosan-based polysaccharide biomaterials in cartilage tissue engineering : a review

Articular cartilage is the highly specialized connective tissue of diarthrodial joints. Its principal function is to provide a smooth, lubricated surface for articulation and to facilitate the transmission of loads with a low frictional coefficient (Figure 1). Articular cartilage is devoid of blood vessels, lymphatics, and nerves and is subject to a harsh biomechanical environment. Most important, articular cartilage has a limited capacity for intrinsic healing and repair. In this regard, the preservation and health of articular cartilage are paramount to joint health.



Figure 1.

Gross photograph of healthy articular cartilage in an adult human knee.



Injury to articular cartilage is recognized as a cause of significant musculoskeletal morbidity. The unique and complex structure of articular cartilage makes treatment and repair or restoration of the defects challenging for the patient, the surgeon, and the physical therapist. The preservation of articular cartilage is highly dependent on maintaining its organized architecture.

/pdf/the-basic-science-of-articular-cartilage-structure-3mc2a5lzti.pdf

The basic science of articular cartilage: structure, composition, and function

ARTICULAR cartilage contains a high concentration of acid glycosaminoglycans (GAG), reaching 6% by wet weight and associated with fixed charge densities up to 0.2 mEq g−1. This leads to considerable swelling pressure within cartilage, due to, first, the strongly non-ideal osmotic pressure, characteristic of polymer solutions, which increases sharply with concentration and, second, the ionic contribution, in accordance with the Gibbs-Donnan equilibrium. Ogston and Wells1–3 have estimated the values of these two components and I have calculated them from my experimental data on cartilage4,5. The two components of swelling pressure are approximately of the same order of magnitude and can reach values as high as 1.7kgcm−2 (refs 4 and 5). Since normal cartilage does not swell in solution, even when it is removed from the joint and cut into thin (250 µm) slices (lowest curve, Fig. 1), this implies that its high swelling pressure must be counteracted by considerable elastic forces within the collagen fibre network. It has been known for some time that the concentration of GAG gradually increases from the articular surface to the deep zone (for example, refs 6 and 7). A typical variation of total GAG content with depth, measured as fixed charge density, is shown in Table 1. I now suggest that this particular profile is adapted to the physiological function and mechanical properties of cartilage.

Balance between swelling pressure and collagen tension in normal and degenerate cartilage

Post-mortem specimens of the human lumbar (L4-L5) intervertebral disc have been studied histologically and physico-chemically. Blood vessels were found only at the margin of the anulus fibrosus and in the vertebral marrow spaces. Contact between disc tissue and marrow spaces occupied about 10% of the bone-cartilage interface. The disc was most cellular at the periphery of the anulus fibrosus and in the hyaline cartilage next to the vertebral bone. Cellularity declined towards the nucleus pulposus where it achieved a low constant value. The cell density of the disc as a whole was about 60000 cells/mm3. For glucose, the diffusion coefficient of the anulus fibrosus and hyaline cartilage end plate was 2.5 cm2/sec and 2.4 cm2/sec respectively at 37 degrees C, comparable to that of cartilage elsewhere. The permeability of the bone-cartilage interface was low, particularly in the peripheral part. Calculations, based on the present findings and derived values for glucose utilization in disc tissue, indicate that nutritional conditions in the intervertebral disc are more critical than, for example, in articular cartilage.

Factors involved in the nutrition of the human lumbar intervertebral disc: cellularity and diffusion of glucose in vitro.

The metabolism of the canine nucleus pulposus was investigated at different oxygen tensions. It was found that even at high oxygen tensions the metabolism is mainly anaerobic, only approximately 1.5% of the glucose being converted to carbon dioxide. The concentration dependence of oxygen consumption is limited to very low oxygen tensions. Values of oxygen consumption and lactic acid production were used to calculate the concentration profiles of these substances within the nucleus pulposus, using a diffusion theory. The predicted concentration profiles were compared with the experimental measurements of concentration at various positions in the disc. The good agreement in these values found in the nucleus confirms that the main mechanism of metabolite transport is diffusion, and the main route of nutrient supply into the nucleus is via the endplate.

Nutrition of the intervertebral disc: solute transport and metabolism.

Objective. Age is an important risk factor for osteoarthritis (OA). During aging, nonenzymatic glycation results in the accumulation of advanced glycation end products (AGEs) in cartilage collagen. We studied the effect of AGE crosslinking on the stiffness of the collagen network in human articular cartilage. Methods. To increase AGE levels, human adult articular cartilage was incubated with threose. The stiffness of the collagen network was measured as the instantaneous deformation (ID) of the cartilage and as the change in tensile stress in the collagen network as a function of hydration (osmotic stress technique). AGE levels in the collagen network were determined as: Ne-(carboxy[m]ethyl)lysine, pentosidine, amino acid modification (loss of arginine and [hydroxy-]lysine), AGE fluorescence (360/460 nm), and digestibility by bacterial collagenase. Results. Incubation of cartilage with threose resulted in a dose-dependent increase in AGEs and a concomitant decrease in ID (r = -0.81, P < 0.001; up to a 40% decrease at 200 mM threose), i.e., increased stiffness, which was confirmed by results from the osmotic stress technique. The decreased ID strongly correlated with AGE levels (e.g., AGE fluorescence r = -0.81, P < 0.0001). Coincubation with arginine or lysine (glycation inhibitors) attenuated the threose-induced decrease in ID (P < 0.05). Conclusion. Increasing cartilage AGE crosslinking by in vitro incubation with threose resulted in increased stiffness of the collagen network. Increased stiffness by AGE crosslinking may contribute to the age-related failure of the collagen network in human articular cartilage to resist damage. Thus, the age-related accumulation of AGE crosslinks presents a putative molecular mechanism whereby age is a predisposing factor for the development of OA.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1529-0131%28200201%2946%3A1%3C114%3A%3AAID-ART10025%3E3.0.CO%3B2-P

Crosslinking by advanced glycation end products increases the stiffness of the collagen network in human articular cartilage: A possible mechanism through which age is a risk factor for osteoarthritis

https://content.iospress.com/download?id=10.3233/BIR-1975-123-416

Alice Maroudas

Papers

Balance between swelling pressure and collagen tension in normal and degenerate cartilage

Factors involved in the nutrition of the human lumbar intervertebral disc: cellularity and diffusion of glucose in vitro.

Nutrition of the intervertebral disc: solute transport and metabolism.

Crosslinking by advanced glycation end products increases the stiffness of the collagen network in human articular cartilage: A possible mechanism through which age is a risk factor for osteoarthritis

Biophysical chemistry of cartilaginous tissues with special reference to solute and fluid transport.