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PubMed2006

The collagen structure of the tympanic membrane: collagen types I, II, and III in the healthy tympanic membrane, during healing of a perforation, and during infection.

OBJECTIVE: To analyze the distribution of 3 collagen types in healthy tympanic membranes, during healing of a perforation, and during infection. DESIGN: Immunohistochemical study of collagen types I, II, and III in the tympanic membranes of healthy rats as well as during healing of a perforation and in the presence of infection with Streptococcus pneumoniae at various time points. SETTING: Laboratory research center at a university hospital. RESULTS: Type II collagen was a main constituent of the lamina propria of the pars tensa, whereas type I collagen was found mainly in the pars flaccida. Collagen types I and III were found at the insertion to the malleus handle and in the loose connective tissue surrounding the main collagen layer of the pars tensa. After myringotomy, collagen types I and III were found at the perforation border and around dilated blood vessels early in the healing phase. During infection, the collagen layer was thickened and stained strongly for type II collagen. Collagen types I and III were found in the edematous connective tissue around the main collagen layer and around dilated blood vessels. Three months after perforation or infection, all 3 collagens were present in the lamina propria of the tympanic membrane. Extensive amounts of all 3 collagen types were present in the scar tissue in the tympanic membranes of rats that had undergone myringotomy during the presence of acute otitis media. CONCLUSIONS: The lamina propria of the pars tensa is mainly made up of type II collagen, whereas type I collagen is found in the pars flaccida. Thus the fibrous structure of the pars tensa and flaccida is composed of diverse collagen types, which reflects the different physiological properties of these tissues. Collagen types I and III are present in the acute healing phase after myringotomy and infection, and the collagen content of the tympanic membrane is modified during the inflammatory and healing process.

Animals↗
PubMed1988

A monoclonal anti-type II collagen antibody with cross-reactive anti-Ig activity specific for the F(ab')2 fragment.

An IgG2a hybridoma antibody (BC-10) was obtained by a myeloma fusion with lymphocytes from B10.RIII mice immunized against native bovine type II collagen. This anti-collagen monoclonal exhibited extensive cross-reactivity with several type II collagen species. BC-10 was found to have self-associating properties, but not the specificity of a typical IgG rheumatoid factor, inasmuch as this mAb bound to F(ab')2 fragments of itself and of normal mouse IgG. Self binding was inhibited by the association of BC-10 with type II collagen, and inhibition assays indicated that antibodies with the capacity to inhibit BC-10 binding to collagen were present in the sera from B10.RIII arthritic mice, but not from DBA/1 LacJ arthritic mice. Joint inflammation and histopathologic features consistent with arthritis were observed in mice injected with the BC-10 hybridoma.

Animals↗
PubMed2004

Markers for type II collagen breakdown predict the effect of disease-modifying treatment on long-term radiographic progression in patients with rheumatoid arthritis.

OBJECTIVE: To investigate in a randomized clinical trial setting with an aggressive combination-therapy arm and a mild-monotherapy arm, whether therapy-induced changes in urinary C-terminal crosslinking telopeptide of type I collagen (CTX-I) and type II collagen (CTX-II) predict 5-year radiographic progression in patients with rheumatoid arthritis (RA). METHODS: Patients had participated in the COBRA (Combinatietherapie Bij Reumatoïde Artritis) trial comparing aggressive step-down combination therapy (the COBRA regimen, including temporary high-dose prednisolone, temporary low-dose methotrexate, and sulfasalazine [SSZ]) and mild monotherapy (SSZ). Urinary CTX-I and CTX-II levels were measured at baseline and 3, 6, 9, and 12 months after initiation of treatment. Radiographs were scored according to the modified Sharp/van der Heijde method (mean of 2 independent readers who were aware of the sequence). Individual long-term radiographic progression was estimated, using baseline radiographs and all radiographs obtained during the followup period, by simple linear regression analysis (curve fitting). RESULTS: Both COBRA therapy and SSZ monotherapy produced a significant decrease in urinary CTX-I and CTX-II levels at 3 months, and this decrease was amplified at 6 months. COBRA therapy suppressed CTX-II (change from baseline levels -36% and -43% at 3 and 6 months, respectively), but not CTX-I, significantly better than did SSZ (-17% and -21% at 3 and 6 months, respectively) at 3 and 6 months. The magnitude of the decrease in urinary CTX-II levels at 3 months significantly predicted long-term (5-year) radiographic progression (beta = 0.48 [95% confidence interval (95% CI) 0.13, 0.83]). This effect was independent of the change in disease activity and inflammation indices at 3 months. Patients whose CTX-II levels were normalized (<150 ng/mmoles of urinary creatinine) at 3 months had a significantly higher chance of radiographic stability (no progression over 5 years) than did patients whose CTX-II levels were increased both at baseline and at 3 months (odds ratio 4.5 [95% CI 1.5, 13]). CONCLUSION: The individual CTX-II response measured after 3 months of therapy in patients with active RA who had increased CTX-II levels at baseline independently predicts long-term radiographic progression. Urinary CTX-II levels may be used as early markers of treatment efficacy in patients with RA.

Adult↗
PubMed1991

Absence of autoimmunity to type II collagen in generalised nodal osteoarthritis.

A cardinal feature of generalised nodal osteoarthritis is the loss of articular cartilage. To determine if autoimmunity to these cartilage collagens occurred, serum antibodies to native and denatured type II collagen were measured by enzyme linked immunosorbent assay (ELISA) in 96 patients (90 women, six men, aged 47-91 years) with generalised nodal osteoarthritis. Generalised nodal osteoarthritis was diagnosed by typical clinical and radiological features. Serum samples from 42 blood donors were assayed as controls. No significant difference was found between the patients with generalised nodal osteoarthritis and the controls. Furthermore, the 20 patients who were HLA-A1, B8 positive had similar antibody levels to the group as a whole. One woman patient with generalised nodal osteoarthritis (HLA-A1, B8 negative) had markedly increased antibody levels to native and denatured type II collagen in a pattern similar to that seen in patients with rheumatoid arthritis. This patient did not develop super added rheumatoid arthritis during a three year follow up period. Autoimmunity to type II collagen is therefore rare in generalised nodal osteoarthritis. A lack of collagen antibodies in a condition characterised by hyaline cartilage loss suggests that the presence of such antibodies in rheumatoid arthritis is more than a secondary event to joint damage.

Aged↗
PubMed1984

Arthritis induced in rats by cloned T lymphocytes responsive to mycobacteria but not to collagen type II.

We have been studying the pathogenesis of adjuvant arthritis in rats using a long-term cell line of T lymphocytes, the A2 line, which can induce polyarthritis and can also be used to vaccinate rats against adjuvant arthritis. Although line A2 was selected for its proliferative response to mycobacteria, it also responded to collagen type II. To elucidate its role of responsiveness to collagen type II and the relationship between arthritogenicity and vaccination, we cloned A2 and selected a subline A2b. We now report that subline A2b, which bore a marker of helper/delayed hypersensitivity T lymphocytes, was strongly arthritogenic, but could not vaccinate against arthritis. Moreover, A2b showed no response to collagen type II. Therefore, reactivity to collagen type II is not a requisite for arthritogenicity, and mediation of arthritis and vaccination can be distinct properties of different populations of T lymphocytes.

Animals↗
PubMed2003

The release of crosslinked peptides from type II collagen into human synovial fluid is increased soon after joint injury and in osteoarthritis.

OBJECTIVE: To determine concentrations of crosslinked C-telopeptide fragments of type II collagen (CTX-II) in synovial fluid (SF) from patients with joint injury, osteoarthritis (OA), or other knee arthritides. METHODS: Two study groups were used: a cross-sectional group, which included healthy-knee volunteers (reference group [REF]) and patients with pseudogout (PPA), an anterior cruciate ligament tear with or without a meniscus tear (INJ), or primary knee OA (POA); and a longitudinal group, which included patients with arthroscopic cartilage changes or septic arthritis. CTX-II was quantified by competition enzyme-linked immunosorbent assay (ELISA) based on a monoclonal antibody that recognized the C-terminus of the peptide EKGPDP as a proteolytic neoepitope. Aggrecan fragments, matrix metalloproteinases 1 and 3, and tissue inhibitor of metalloproteinases 1 were determined by ELISAs. RESULTS: Concentrations of CTX-II in SF were higher in patients with PPA, INJ, and POA than in the REF group (P < 0.001). After joint injury, mean levels of CTX-II in SF were increased above REF levels at all time intervals (P < 0.001), and were highest within hours after trauma. In those in the longitudinal study group with joint cartilage damage, variation coefficients for CTX-II were 81% (between patients) and 64% (within patient), monitored over 1 year. In a patient with septic arthritis, SF CTX-II increased at the onset of symptoms, and peaked 30-fold higher than the baseline. Concentrations of all biomarkers decreased with successful treatment. CONCLUSION: This is the first report to describe the release into SF of soluble molecular fragments specific for the degradation of mature, crosslinked, type II collagen (CII) in human OA and joint injury. The results provide strong evidence that the integrity of the CII network of cartilage is compromised soon after joint injury and in arthritis. This early degradation of CII may represent an important treatment target.

Adolescent↗
PubMed1990

Tandem duplication within a type II collagen gene (COL2A1) exon in an individual with spondyloepiphyseal dysplasia.

We have characterized a mutation in the type II collagen gene (COL2A1) that produces a form of spondyloepiphyseal dysplasia. The mutation is an internal tandem duplication of 45 base pairs within exon 48 and results in the addition of 15 amino acids to the triple-helical domain of the alpha 1 chains of type II collagen derived from the abnormal allele. Although the repeating (Gly-Xaa-Yaa)n motif that characterizes the triple-helical domain is preserved, type II collagen derived from cartilage of the affected individual contains a population with excessive posttranslational modification, consistent with a disruption in triple-helix structure. The mutation is not carried by either parent, indicating that the phenotype in the affected individual is due to a new dominant mutation. DNA sequence homology in the area of the duplication suggests that the mutation may have arisen by unequal crossover between related sequences, a proposed mechanism in the evolution and diversification of the collagen gene family.

Alleles↗
PubMed2006

Anabolic and catabolic function of chondrocyte ex vivo is reflected by the metabolic processing of type II collagen.

OBJECTIVE: The aim of the present study was to investigate collagen metabolism after anabolic and catabolic stimulation of chondrocytes ex vivo. DESIGN: Metabolic activities in ex vivo bovine cartilage explants were stimulated with insulin-like growth factor I (IGF-I) or a combination of tumor necrosis factor alpha (TNFalpha) and oncostatin M (OSM). Supernatants were assessed for changes in biochemical markers, N-terminal propeptide of type II (PIINP) collagen and fragments of C-telopeptide of type II collagen (CTX-II). Matrix metalloproteinases (MMP) were added to metabolic inactivated cartilage and evaluated by the two biochemical markers for formation or degradation, respectively. Finally, urinary CTX-II and PIINP were evaluated for assessment of type II collagen turnover in patients with rheumatoid arthritis (RA). RESULTS: In the bovine articular cartilage explants, IGF-I induced an increase in PIINP level up to 4.8+/-1.1[ng/ml]/mg cartilage whereas CTX-II remained below 0.1+/-0.1[ng/ml]/mg cartilage. In the catabolic stimulated explants both PIINP and CTX-II were released to the supernatant, reaching concentrations of 9.0+/-1.4 and 9.1+/-2.2[ng/ml]/mg cartilage, respectively. RA patients had significantly lower serum concentrations of PIINP (3.4+/-3.7 ng/ml) compared with those healthy individuals (18.7+/-12.41 ng/ml, P<0.001). In contrast, RA patients had significantly higher urinary CTX-II (0.8+/-0.8 mg/mmol) compared to the healthy controls (0.1+/-0.08 mg/mmol, P=0.004). CONCLUSIONS: This study is the first to demonstrate that precursors and degradation products of type II collagen released into the supernatant can effectively reflect the anabolic and catabolic activities of stimulated cartilage explants.

Animals↗
PubMed2006

[Significance of citrullinated collagen type II and its antibodies in rheumatoid arthritis].

OBJECTIVE: To investigate the significance of citrullinated collagen type II and its antibodies in the pathogenesis and diagnosis of rheumatoid arthritis (RA). METHODS: Serum samples were obtained from 175 patients with RA, 112 patients with systemic lupus erythematosus (SLE), 37 patients with osteoarthritis (OA), and 160 healthy controls. Arginine residues of bovine collagen type II (bCII) were converted to citrulline residues by peptidylarginine deiminase (PAD). The presence of antibodies against citullinated bCII (Cit-bCII) and bCII, a substrate protein of PAD, were examined by using enzyme-linked immunosorbent assay (ELISA) and Western blotting. The levels of anti-cyclic citrullinated peptide (CCP) antibodies, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) in the above patients were detected. RESULTS: The positive rate of anti-CitbCII antibodies of the RA patients was 50.3% (88/175), significantly higher than those of the SLE patients (17.9%, 20/112), OA patients (18.9%, 7/37), and healthy controls (2.5%, 4/160). The positive rate of anti-b of the RA patients was 33.7% (59/175), significantly lower than that of the CII antibodies. The levels of anti-CitbCII and anti-bCII antibodies were not statistically different from SLE and OA patients. There was a close correlation between anti-CitbCII and anti-CCP antibodies. Spearman correlation analysis showed that anti-CitbCII antibodies were positively correlated with anti-CCP antibodies, and CRP, ESR, RF, X ray imaging, course of disease, and age were not associated with anti-CitbCII antibodies. CONCLUSION: Anti-citrullinated bCII antibody is relatively RA-specific. Citrullination appears to be important in RA.

Adult↗
PubMed1992

Localization of type II collagen, long form alpha 1(IX) collagen, and short form alpha 1(IX) collagen transcripts in the developing chick notochord and axial skeleton.

In this study we compare, by in situ hybridization, the spatial and temporal expression patterns of transcripts of avian type II collagen and the long and short forms of the (alpha 1) chain of type IX collagen during the development of the notochord and axial skeleton. We observed type II collagen and short form type IX collagen transcripts in the developing (stage 25-28) nonchondrogenic notochord. Conversely, long form type IX transcripts were not detectable in the notochord or perinotochordal sheath. Interestingly, all three transcripts colocalized in the developing chondrogenic vertebrae of the axial skeleton as well as in the chondrocranium and Meckel's cartilage. The expression of the short form of type IX collagen in these regions was more restricted than that of the long form. This report provides additional support for a complex regulatory pathway of cartilage marker gene expression in chondrogenic vs. nonchondrogenic tissues during avian embryogenesis.

Animals↗
PubMed2002

The safety and efficacy of chicken type II collagen on uveitis associated with juvenile rheumatoid arthritis.

PURPOSE: To investigate the safety and efficacy of chicken type II collagen in treating uveitis associated with juvenile rheumatoid arthritis (JRA). METHODS: A prospective dose-ranging (60 and 540 microg) pilot study of orally administered chicken type II collagen in 13 participants, aged 2-18 years, with JRA and uveitis and without prior exposure to collagens. Anterior chamber cells, flare, vitreous haze, visual acuity, and concomitant anti-inflammatory medications were the ophthalmic outcomes. Arthritis outcomes included the American College of Rheumatology (ACR) core set. RESULTS: No serious or related adverse events were reported. Four participants (2 low dose, 2 high dose) experienced improvement in ophthalmic outcome, while two participants (1 in each group) worsened (p > 0.5). According to ACR criteria, six participants showed improvement in JRA. CONCLUSIONS: Although appearing safe, clearly demonstrating the efficacy of this treatment for JRA or uveitis remains a challenge. Based on the results from this pilot study, a large positive treatment effect on uveitis is unlikely.

Administration, Oral↗
PubMed2001

Cartilage-specific autoimmunity in rheumatoid arthritis: characterization of a triple helical B cell epitope in the integrin-binding-domain of collagen type II.

Cartilage-specific proteins are considered potential autoantigens that could continuously fuel autoimmune responses directed to the joints in rheumatoid arthritis (RA). Using recombinant chimeric collagen type II we have identified one major type II collagen (CII) epitope (denoted U1) recognized by RA sera. The U1 epitope is a triple helical structure formed by 11 amino acids (triple helical position 494-504) and colocalizes with the recently described alpha1beta1/alpha2beta1 integrin binding site. It is a major epitope, found in 14/22 RA sera positive for antibodies to CII. One individual could be followed for a long time and the results showed that IgG antibodies specific for the U1 epitope were maintained along the chronic disease course but suppressed during periods of cyclosporin A and anti-CD4 treatment. We also found that the U1 epitope was recognized in rats susceptible to collagen-induced arthritis. A monoclonal autoantibody (mAb 126.30) was raised from DA rats, which bound the same epitope. The antibodies bound the cartilage in vivo showing that the epitope is exposed to the immune system for immune complex formation in the intact joint.

Animals↗
PubMed1985

Autoimmunity to native type II collagen--a distinct genetic subset of rheumatoid arthritis.

HLA phenotypes were determined in 60 Caucasoid patients with rheumatoid arthritis (RA) and normal serum antibody levels to native type II collagen. Antigen frequencies were compared with 52 patients with RA who had elevated antibody levels to native type II collagen. Both RA groups were compared with 163 healthy controls. A clinical comparison of both RA groups yielded few differences, except a decreased incidence of rheumatoid factor and a positive family history of RA and radiologically, increased osteosclerosis in the RA group with elevated antibodies to native type II collagen. HLA-DR4 was increased and HLA-DR7 was decreased in the RA group with normal antibody levels to native type II collagen. A comparison of both RA groups showed an increased incidence of HLA-DR4 in the normal antibody group, whereas HLA-DR7 was increased in the elevated antibody group. In the elevated antibody group the majority of patients possessed either HLA-DR3 or DR7 both of which are in strong linkage disequilibrium with HLA-DQw2. This immunogenetic data suggests that RA patients with autoimmunity to native II collagen form a distinct genetic subset of RA.

Adolescent↗
PubMed1986

Isolation and purification of cyanogen bromide-derived peptides of type II collagen directly from tissue (Swarm chondrosarcoma).

A preparative procedure is described for isolating type II collagen-fragments directly from tissue. Swarm chondrosarcoma from rat, a cartilagenous tissue rich in type II collagen, was digested by cyanogen bromide in 70% formic acid. The resulting crude extract was desalted (G 25 column chromatography) and lyophylized. The yield of peptide mixture was about 1 250 mg obtained from 100 g tissue. The method of purification commonly used for type II collagen prior to cyanogen bromide-cleavage yielded 20 mg peptides from 100 g tissue. Separation of the cyanogen bromide-derived fragments was performed by gel filtration. The column was run at 43 degrees C (denaturing-temperature of collagens) to avoid fibril formation, and a volatile buffer was used (ammonium formate buffer, pH 7.5) so that the effluent fractions could be easily lyophylized. Two-dimensional gel electrophoresis of the main peaks of the column profile demonstrated that this purification step resulted in a good separation of the fragment mixture, although additional steps may be necessary for complete separation of the peptides. The most striking advantages of the method for direct digestion of tissue outlined here are the increase in yield (about 60-fold) and the reduction of purification steps (avoiding type II collagen purification).

Animals↗
PubMed2003

Immunohistochemical distribution patterns of collagen type II, chondroitin 4-sulfate, laminin and fibronectin in human nasal septal cartilage.

Collagen type II, chondroitin 4-sulfate, laminin and fibronectin are major components of cartilage matrix. It is important to know their distribution patterns to evaluate relationships between cartilage cells and surrounding cartilage matrix. In the present study, we investigated localization patterns of these macromolecules in human nasal septal cartilage by immunohistochemical methods. Samples of human nasal septal cartilage were obtained from patients with nasal septum deviations who underwent septoplastic operation and were prepared for immunohistochemical examination. Distribution patterns of cartilage matrix macromolecules correlated with those found in other cartilage tissues. Diffuse staining of collagen type II was found in the cartilage matrix, chondroitin 4-sulfate immunostaining was present in the cytoplasm and like a pericellular ring around chondrocytes. Laminin immunostaining was found in the cytoplasm of chondrocytes, and fibronectin was localized in the pericellular matrix and in capsules of human nasal septal cartilage. Moreover, fibronectin was also detected at high levels in the interconnecting segments between adjacent chondrons. In conclusion, similar localisation patterns of the components investigated in human septal cartilage as in other tissues indicate that these macromolecules may play a role in both cell-matrix adhesion and matrix-matrix cohesion in the pericellular microenvironment surrounding nasal septal cartilage chondrocytes as in other cartilage tissues.

Adult↗
PubMed1998

Effect of type II collagen in chondrocyte response to TGF-beta 1 regulation.

The in vivo role of the extracellular matrix and the manner in which it interfaces with soluble regulators remains unknown. This study reports the modulation by extracellular type II collagen of TGF-beta 1-stimulated DNA synthesis, proteoglycan synthesis, and mRNA expression for alpha 1(II) procollagen and aggrecan core protein in the adult articular chondrocyte. Bovine chondrocytes were isolated and resuspended in alginate beads which contained increasing amounts of type II collagen from 0 to 1.5% (w/v). Cultures were maintained for 7 days in basal, DMEM, TGF-beta 1 (10 ng/ml), or FBS (10%) supplemented medium. DNA and proteoglycan synthesis were determined by radiotracer incorporation. The relative amounts of mRNA were analyzed by Northern blot analysis. Exogenous collagen increased DNA synthesis in all culture conditions beginning at concentrations of 0.75% (w/v). We observed that extracellular type II collagen augments both TGF-beta 1 stimulated increases of aggrecan gene expression up to 400% and alpha 1(II) procollagen gene expression up to 180% in a dose-dependent fashion. This is distinct from cultures which were either basal or FBS supplemented medium which lacked a dose-dependent change in aggrecan gene expression and demonstrated a decrease in alpha 1(II) procollagen gene expression. Exogenous collagen above 0.75% (w/v) increased proteoglycan synthesis significantly in FBS and TGF-beta 1-stimulated cultures but not in basal cultures. We have demonstrated that the alterations in gene expression that occur in response to TGF-beta 1 are modulated by extracellular type II collagen. This modulation is possible through both transcriptional and posttranscriptional regulatory mechanisms.

Aggrecans↗
PubMed2000

The transcription factor deltaEF1 is inversely expressed with type II collagen mRNA and can repress Col2a1 promoter activity in transfected chondrocytes.

The regulation of Col2a1, which encodes type II collagen, likely results from a balance of both positive and negative proteins. Here we present evidence that the transcription factor deltaEF1 participates in the negative regulation of Col2a1 transcription. A deletion analysis suggested that a region between -100 and -307 of the rat Col2a1 gene was required for activity in differentiating chick limb bud mesenchymal cells; however, mutation of a conserved E2 box site in this region actually increased promoter activity. Supershift analysis demonstrated that deltaEF1, a known transcriptional repressor, bound to the E2 box in a sequence-dependent manner. Chick limb bud mesenchymal cells, which do not express type II collagen, expressed abundant deltaEF1 mRNA, but, following differentiation in micromass culture, deltaEF1 mRNA expression was lost. Primary embryonic chick sternal chondrocytes, which express abundant type II collagen, displayed minimal levels of deltaEF1 mRNA. The inhibition of Col2a1 transcription following treatment of chick sternal chondrocytes with growth factors was accompanied by increased deltaEF1 expression. Overexpression of deltaEF1 in differentiated chondrocytes resulted in decreased expression of a reporter construct containing a collagen II promoter/enhancer insert; however, this negative regulation was not dependent on the proximal E2 box. This is the first report of a specific transcription factor involved in the negative regulation of Col2a1.

Animals↗
PubMed2004

Type II collagen accumulation in overlying dermo-epidermal junction of pilomatricoma is mediated by bone morphogenetic protein 2 and 4.

Pilomatricoma consists of the cells differentiating towards hair matrix cells. Immunohistochemical study revealed the deposition of type II collagen in the overlying dermo-epidermal junction (DEJ) of this benign tumor. Proalpha(1)(II) mRNA was detected by RT-PCR in the overlying epidermal layer but not in the dermal layer prepared from the lesional skin of pilomatricoma. The neutral salt-soluble proteins extracted from the tumor of pilomatricoma induced proalpha(1)(II) mRNA in the cultured human keratinocytes but not in the cultured dermal fibroblasts. Bone morphogenetic protein 2 or 4 (BMP2 or 4) was immunohistochemically detected in some shadow cells of pilomatricoma. Recombinant BMP2 and BMP4 were found to induce proalpha(1)(II) mRNA concentration dependently in the cultured human keratinocytes but not in the cultured fibroblasts. Proalpha(1)(II) mRNA induced by BMP2 and in cultured keratinocytes contained exon 2, indicating that the mRNA species is non-chondrogenic type IIA form. The results strongly suggest that BMP2 or 4 expressed in pilomatricoma is responsible for the induction of proalpha(1)(II) collagen mRNA in the overlying epidermal cells resulting in the deposition of type II collagen in the DEJ. When human keratinocytes were cultured on type II collagen substratum in vitro, the cell proliferation was accelerated at the early period of culture but was inhibited at the late period of culture, whereas the cell proliferation was persistently accelerated by type I or IV collagen substratum. Type II collagen deposition in the DEJ may potentially exert profound effects on keratinocyte proliferation and differentiation.

Adolescent↗