Anthony P. Hollander

Bio: Anthony P. Hollander is an academic researcher from University of Liverpool. The author has contributed to research in topics: Cartilage & Type II collagen. The author has an hindex of 48, co-authored 95 publications receiving 10270 citations. Previous affiliations of Anthony P. Hollander include University of Bristol & University of Sheffield.

The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration.

Abstract: Very little is known about the turnover of extracellular matrix in the human intervertebral disc. We measured concentrations of specific molecules reflecting matrix synthesis and degradation in predetermined regions of 121 human lumbar intervertebral discs and correlated them with ageing and Thompson grade of degeneration. Synthesis in intervertebral discs, measured by immunoassay of the content of a putative aggrecan biosynthesis marker (846) and the content of types I and II procollagen markers, is highest in the neonatal and 2-5-yr age groups. The contents of these epitopes/molecules progressively diminished with increasing age. However, in the oldest age group (60-80 yr) and in highly degenerated discs, the type I procollagen epitope level increased significantly. The percentage of denatured type II collagen, assessed by the presence of an epitope that is exposed with cleavage of type II collagen, increased twofold from the neonatal discs to the young 2-5-yr age group. Thereafter, the percentage progressively decreased with increasing age; however, it increased significantly in the oldest group and in highly degenerate discs. We identified three matrix turnover phases. Phase I (growth) is characterized by active synthesis of matrix molecules and active denaturation of type II collagen. Phase II (maturation and ageing) is distinguished by a progressive drop in synthetic activity and a progressive reduction in denaturation of type 11 collagen. Phase III (degeneration and fibrotic) is illustrated by evidence for a lack of increased synthesis of aggrecan and type II procollagen, but also by an increase in collagen type II denaturation and type I procollagen synthesis, both dependent on age and grade of tissue degeneration.

Increased damage to type II collagen in osteoarthritic articular cartilage detected by a new immunoassay.

Abstract: A new immunoassay was developed to detect denaturation of type II collagen in osteoarthritis (OA). A peptide, alpha 1 (II)-CB11B, located in the CB11 peptide of type II collagen, was synthesized and used to produce a monoclonal antibody (COL2-3/4m) of the IgG1 (kappa) isotype. This reacts with a defined epitope in denatured but not native type II collagen and the alpha 3 chain of type XI collagen. The latter is present in very small amounts (about 1% wt/wt) in cartilage relative to the alpha 1 (II) chain. By using an enzyme-linked immunosorbent assay, type II collagen denaturation and total type II collagen content were determined. The epitope recognized by the antibody was resistant to cleavage by alpha-chymotrypsin and proteinase K which were used to extract alpha 1 (II)-CB11B from the denatured (alpha-chymotrypsin soluble) and residual native (proteinase K soluble) collagen alpha-chains, respectively, present in human femoral articular cartilage. Type II collagen content was significantly reduced from a mean (range) of 14% (9.2-20.8%) of wet weight in 8 normal cartilages to 10.3% (7.4-15.0%) in 16 OA cartilages. This decrease, which may result in part from an increased hydration, was accompanied by an increase in the percent denaturation of type II collagen in OA to 6.0% of total type II collagen compared with 1.1% in normal tissue. The percent denaturation was ordinarily greater in the more superficial zone than in the deep zone of OA cartilage.

Histological assessment of cartilage repair: a report by the Histology Endpoint Committee of the International Cartilage Repair Society (ICRS).

Abstract: Physical injury frequently causes tissue damage, including laceration. Repair of the damage usually results in the formation of a scar; complete anatomic healing and true regeneration are rare. Connective tissues tend to heal naturally and successfully only if the injury is minor. If the damage is more severe, then a good functional result can be achieved only if Nature is assisted by surgical intervention. The efficacy of such measures has been established in the cases of bone and tendon injuries but not in the case of cartilage damage 1. In the latter situation, we are still prejudiced by Hippocrates' opinion that "ulcerated cartilage is universally allowed to be a troublesome disease." 2 In addition, our view is necessarily colored by the scarcity of successful therapeutic modalities 3. Articular cartilage is a narrow layer of specialized connective tissue that permits smooth, frictionless movement of diarthrodial joints. It is comprised of a relatively small number of cells (chondrocytes) embedded in an abundant extracellular matrix 4. The latter consists predominantly of type-II collagen, proteoglycans, and water, along with smaller amounts of other collagen types and noncollagenous proteins. Histologically, articular cartilage is divided into three zones, which are distinguished by the shape of the chondrocytes and the arrangement of type-II collagen fibers. The superficial zone is characterized by flattened disc-like chondrocytes, a low proteoglycan content, and densely-packed, horizontally-arranged collagen fibrils of uniform diameter. This layer has been described as a tension-resisting diaphragm 5 by virtue of its tendency to curl when the articular cartilage is released from the subchondral bone 6. In the middle zone, chondrocytes attain a more rounded profile, proteoglycan content increases, and the collagen fibers decussate to provide an oblique transitional network between the superficial tangential zone and the deep radial zone. The deep radial zone is …

Damage to type II collagen in aging and osteoarthritis starts at the articular surface, originates around chondrocytes, and extends into the cartilage with progressive degeneration.

Abstract: Enhanced denaturation of type II collagen fibrils in femoral condylar cartilage in osteoarthritis (OA) has recently been quantitated immunochemically (Hollander, A.P., T.F. Heathfield, C. Webber, Y. Iwata, R. Bourne, C. Rorabeck, and A.R. Poole. 1994. J. Clin. Invest. 93:1722-1732). Using the same antibody that only reacts with denatured type II collagen, we investigated with immunoperoxidase histochemistry (results were graded for analysis) the sites of the denaturation (loss of triple helix) of this molecule in human aging (at autopsy, n= 11) and progressively degenerate (by Mankin grade [MG]) OA (at arthroplasty, n= 51) knee condylar cartilages. Up to 41 yr, most aging cartilages (3 of 4) (MG 0-4) showed very little denaturation. In most older cartilages, (4 of 7) (MG 2-4), staining was observed in the superficial and mid zones. This pattern of collagen II denaturation was also seen in all OA specimens with increased staining extending to the deep zone with increasing MG. Collagen II staining correlated directly both with MG and collagen II denaturation measured by immunoassay. Cartilage fibrillation occurred in OA cartilages with increased penetration of the staining for collagen II denaturation into the mid and deep zones and where denaturation was more pronounced by immunoassay. Thus in both aging and OA the first damage to type II collagen occurs in the superficial and upper mid zone (low MG) extending to the lower mid and deep zones with increasing degeneration (increasing MG). Initial damage is always seen around chondrocytes implicating them in the denaturation of type II collagen.

The extracellular matrix at a glance

Abstract: ![Figure][1] The extracellular matrix (ECM) is the non-cellular component present within all tissues and organs, and provides not only essential physical scaffolding for the cellular constituents but also initiates crucial biochemical and biomechanical cues that are required for tissue

Growth Factors, Matrices, and Forces Combine and Control Stem Cells

Abstract: Stem cell fate is influenced by a number of factors and interactions that require robust control for safe and effective regeneration of functional tissue. Coordinated interactions with soluble factors, other cells, and extracellular matrices define a local biochemical and mechanical niche with complex and dynamic regulation that stem cells sense. Decellularized tissue matrices and synthetic polymer niches are being used in the clinic, and they are also beginning to clarify fundamental aspects of how stem cells contribute to homeostasis and repair, for example, at sites of fibrosis. Multifaceted technologies are increasingly required to produce and interrogate cells ex vivo, to build predictive models, and, ultimately, to enhance stem cell integration in vivo for therapeutic benefit.