The differentiation of prehypertrophic into hypertrophic chondrocytes drives an OA-remodeling program and IL-34 expression.

OBJECTIVES: We hypothesize that chondrocytes from the deepest articular cartilage layer are pivotal in maintaining cartilage integrity and that the modification of their prehypertrophic phenotype to a hypertrophic phenotype will drive cartilage degradation in osteoarthritis. DESIGN: Murine immature articular chondrocytes (iMACs) were successively cultured into three different culture media to induce a progressive hypertrophic differentiation. Chondrocyte were phenotypically characterized by whole-genome microarray analysis. The expression of IL-34 and its receptors PTPRZ1 and CSF1R in chondrocytes and in human osteoarthritis tissues was assessed by RT-qPCR, ELISA and immunohistochemistry. The expression of bone remodeling and angiogenesis factors and the cell response to IL-1ß and IL-34 were investigated by RT-qPCR and ELISA. RESULTS: Whole-genome microarray analysis showed that iMACs, prehypertrophic and hypertrophic chondrocytes each displayed a specific phenotype. IL-1ß induced a stronger catabolic effect in prehypertrophic chondrocytes than in iMACs. Hypertrophic differentiation of prehypertrophic chondrocytes increased Bmp-2 (95%CI [0.78; 1.98]), Bmp-4 (95%CI [0.89; 1.59]), Cxcl12 (95%CI [2.19; 5.41]), CCL2 (95%CI [3.59; 11.86]), Mmp 3 (95%CI [10.29; 32.14]) and Vegf mRNA expression (95%CI [0.20; 1.74]). Microarray analysis identified IL-34, PTPRZ1 and CSFR1 as being strongly overexpressed in hypertrophic chondrocytes. IL-34 was released by human osteoarthritis cartilage; its receptors were expressed in human osteoarthritis tissues. IL-34 stimulated CCL2 and MMP13 in osteoblasts and hypertrophic chondrocytes but not in iMACs or prehypertrophic chondrocytes. CONCLUSION: Our results identify prehypertrophic chondrocytes as being potentially pivotal in the control of cartilage and subchondral bone integrity. Their differentiation into hypertrophic chondrocytes initiates a remodeling program in which IL-34 may be involved.

Immunofluorescence in psoriasis: studies of immunoglobulins, complement deposits, and three membrane markers.

Sixteen psoriatic patients and 11 control subjects were investigated by immunofluorescence for skin immunoglobulins (IG) and complement (c) deposits and for keratinocyte membrane markers with anti beta 2 microglobulin (beta 2 m) antibodies (Ab), Con A, and pemphigus Ab. IG and/or c deposits were almost constant in involved epidermis. Three patterns were associated: (1) parakeratotic nuclear (dots-dashes), (2) stratum corneum (SC) intercellular (lamellar pattern), (3) vascular (granular or linear deposits in papillary dermal vessels). In uninvolved epidermis nuclear or vascular deposits could occasionally be present but intercellular pattern was never found in SC. Control specimens were always negative. The three surface markers investigated (beta 2 m, Con A receptor, Pemphigus antigen) could be demonstrated on psoriatic keratinocytes with only slight differences in distribution when compared with controls. Thus, by this methodology no important abnormality could be found in psoriatic keratinocyte membrane antigens.

[Serum IgD levels in various dermatoses (author's transl)]. / Le dosage de l'immunoglobuline D sérique dans diverses dermatoses.

Serum IgD levels were determined by radial immunodiffusion among 349 patients with various dermatoses and 40 normal blood donnors. An increase of serum concentrations was found in atopic patients 62,5 p. 100 of which had levels over 50 mg/1 compared to 20 p. 100 in controls. No correlation was found between IgD and IgE levels in these patients. An increase (but statistically not significant) was also found in chronic urticaria whereas levels were normal in acute urticaria. No difference was found in contact dermatitis nor in psoriasis. High levels occurred in most of patients with primo-secondary syphilis and in acne pustulosa, whereas low IgD levels were found in most patients with malignant proliferative diseases (mycosis fongoide, malignant melanoma, carcinoma). However, the number of patients tested in these groups is too small to allow definitive conclusions. In our experience, determination of serum IgD values is not very useful for diagnosis in dermatologic patients.

[Epidermodysplasia verruciformis (2 cases). Immunological study (author's transl)]. / Epidermodysplasie verruciforme (2 observations). Etude immunologique.

Flat wart-like lesions of two patients with epidermodysplasia verruciformis (EDV) were associated with pink, tan or depigmented pityriasis-like macules. There was no familial history nor mental retardation. Human papilloma virus (HPV) type 5 was demonstrated in the two patients and was responsible for the pityriasis-like lesions. Malignancies seem to be closely related to HPV-5 infection since bowenoid transformation occurred in the 2 patients. Immunological studies showed an increase of serum IgE in both patients and an important decrease of IgM in one of them. Most of delayed hypersensitivity skin tests were negative. T-cell percentages (E rosettes) were decreased in one patient, normal for the other one. The mitogenic response to PHA and ConA was markedly depressed in the two patients but returned to normal values in one of them after 3 months of aromatic retinoid (Ro 10-9359) treatment. Beside the viral type, the defect of cell mediated immunity could play an important role in the disease and in the malignant conversion of the lesions. A long-term preventive treatment by retinoic acid derivatives could be of interest for patients with HPV type 5 EDV.

[Acroangiodermatitis developing on paralytic limbs (author's transl)]. / Pseudo-angiosarcomatose de Kaposi sur membre paralytique.

4 cases of acroangiodermatitis developing on paralytic feet are reported. Acroangiodermatitis might be an entity different from Mali's syndrome and Stewart-Bluefarb's syndrome. Paralysis could generate the dermatologic lesions by increasing venous stasis and enhancing arteriovenous channels.

[Metronidazole therapy in rosacea (author's transl)]. / Traitement de la rosacée par le métronidazole.

Metronidazole was administered (500 mg daily the first month, 250 mg daily the second month and, in some cases, 250 mg every other day the following months) to 62 patients suffering from rosacea or perioral dermatitis. 90 p. 100 of them improved within 2 months and Metronidazole was particularly effective against papulo-pustules. Relapses after interruption of treatment seemed to be less frequent than with Tetracycline therapy. Side-effects (gastro-intestinal disturbances) occurred in few patients but long-term tolerance remains uncertain. So, the length of treatment was less than 6 months and the drug was not given to pregnant women.

[Xanthogranuloma in adults. Clinico-pathological study of a case]. / Le xanthogranulome de l'adulte. Etude anatomo-clinique d'un cas.

The authors report a case of naevoxanthoendothelioma in a 58-year-old woman. 24 cases of naevoxanthoendothelioma in adults have already been reported in the literature. If the age of the patient is considered, nosologic problems may arise, especially with the strictly cutaneous reticulohistiocytosis of Senear and Caro. Biological and ultrastructural features allow the authors to develop some hypotheses about pathogenesis of the disease.

[Oral treatment of severe psoriasis with a new aromatic retinoid (Ro 10-9359) (author's transl)]. / Traitement oral des psoriasis graves par un nouveau rétinoide aromatique (Ro 10-9359).

The aromatic retinoic acid derivative Ro 10-9359 was administered orally to 25 severe psoriatic patients (14 with generalized plaques, 7 erythrodermic, 4 pustular). The initial dose was 25 mg/20 kg body weight daily for 4 weeks; afterwards the same posology was given every other day during several months (Max : 18 months). Excellent results were obtained in 16 patients (64 p. 100) particularly in severe erythrodermic and pustular psoriasis. However, under follow-up therapy relapses sometimes occurred leading to temporary resumption of initial posology. The most important side effects are cheilitis, palmoplantar scaling with thinning of the skin, hyperhidrosis and diffuse hair loss. A slight increase of transaminases and of alkaline phosphatases was found in a few patients. The Ro 10-9359 compound is a very useful new therapy of severe psoriasis.