Advances in a Rapidly Emerging Field of Hair Follicle Stem Cell Research

Human skin maintains the ability to regenerate during adulthood, as it constantly renews itself throughout adult life, and the hair follicle (HF) undergoes a perpetual cycle of growth and degeneration. The study of stem cells (SCs) in the epidermis and skin tissue engineering is a rapidly emerging field, where advances have been made in both basic and clinical research. Advances in basic science include the ability to assay SCs of the epidermis in vivo, identification of an independent interfollicular epidermal SC, and improved ability to analyze individual SCs divisions, as well as the recent hair organ regeneration via the bioengineered hair follicular unit transplantation (FUT) in mice. Advances in the clinic include recognition of the importance of SCs for wound repair and for gene therapy in inherited skin diseases, for example epidermolysis bullosa. The study of the HF stem cells (HFSCs) started by identification of epidermal SC in the HF bulge as quiescent »label retaining cells«. The research of these cells emerged rapidly after the identification of bulge cell molecular markers, such as keratin 15 (K15 and CD34 in mice and CD200 in humans, which allowed the isolation and characterization of bulge cells from follicles. This paper provides an overview of the current knowledge on epidermal SCs in the HF, describing their essential characteristics and the control of follicle SCs fate, their role in alopecia, as well as their use in tissue engineering

Plućni tumorleti s okolnim fibroznim tkivom – suspektni karcinom: prikaz slučaja i pregled literature

Pulmonary tumorlets are small, often multiple nodular proliferations of pulmonary neuroendocrine cells. They are common incidental findings in chronic inflammatory pulmonary diseases. They can also be found in normal lung parenchyma and as one part of the continuum known as diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. In many cases, they are incidental histologic findings of no importance or clinical consequences, or they can be associated with a very slow progression of either obstructive or mixed obstructive/restrictive impairment with good prognosis. Only rarely, they metastasize to an adjacent lymph node or produce ectopic neuroendocrine products. When found during diagnostic examination, they represent a doubt to be a malignant tumor until proven otherwise, which is often impossible without biopsy or surgical removal of the adjacent lung lobe. Hereby, we present a patient with a persistent nodular lung structure after being treated for nonspecific symptoms, cough with non purulent sputum and pain among the scapulae, for a period of one month. He had otherwise normal clinical and laboratory findings, except for a mild mixed obstructive/restrictive pattern of impairment that was shown by lung spirometry. After 8 months, he underwent lobectomy of the medial lobe of the lung with partial lymphadenectomy, since the diagnostic methods applied could not define the nature of lung nodular infiltration. Histologic examination showed a few tumorlets surrounded by the fibrous tissue with a very dense lymphocyte infiltration. We present a review of the literature and emphasize the necessity to include tumorlets with adjacent fibrosis as part of the differential diagnosis of a solitary nodular lung structure.Plućni tumorleti su malene, često višestruke nodularne proliferacije plućnih neuroendokrinih stanica te su čest slučajni nalaz kod kroničnih upalnih plućnih bolesti. Također se mogu naći u normalnom plućnom parenhimu te kao jedan dio kontinuuma poznatog kao difuzna idiopatska hiperplazija plućnih neuroendokrinih stanica. U mnogim slučajevima oni su slučajni histološki nalaz bez značenja ili kliničkih posljedica, a mogu biti i povezani s vrlo sporom progresijom opstruktivnog ili miješanog opstruktivno-restriktivnog oštećenja s dobrom prognozom. Samo rijetko metastaziraju u obližnje limfne čvorove ili stvaraju ektopične neuroendokrine produkte. Nađeni tijekom dijagnostičkog pregleda, predstavljaju sumnju na maligni tumor sve dok se ne dokaže suprotno, što je često nemoguće bez biopsije ili kirurškog odstranjenja pripadajućeg plućnog režnja. Prikazuje se bolesnik s ustrajnim čvorom unutar plućnog parenhima nakon što je tijekom mjesec dana bio liječen zbog nespecifičnih simptoma – kašlja bez gnojnog iskašljaja i boli između lopatica. Ostali su klinički i laboratorijski nalazi bili uredni osim blagog miješanog opstruktivno-restriktivnog oštećenja. Nakon 8 mjeseci odstranjen je srednji režanj pluća zajedno s dijelom limfnih čvorova, jer primijenjene dijagnostičke metode nisu mogle odrediti prirodu čvoraste infiltracije pluća. Histološki pregled je pokazao nekoliko tumorleta okruženih fibroznim tkivom uz vrlo gustu infiltraciju limfocitima. U ovom članku donosimo pregled literature te prikaz slučaja koji naglašava neophodnost uključivanja tumorleta s okolnim fibroznim tkivom u diferencijalnu dijagnozu solitarne nodularne strukture u plućima

Plućni tumorleti s okolnim fibroznim tkivom – suspektni karcinom: prikaz slučaja i pregled literature

Pulmonary tumorlets are small, often multiple nodular proliferations of pulmonary neuroendocrine cells. They are common incidental findings in chronic inflammatory pulmonary diseases. They can also be found in normal lung parenchyma and as one part of the continuum known as diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. In many cases, they are incidental histologic findings of no importance or clinical consequences, or they can be associated with a very slow progression of either obstructive or mixed obstructive/restrictive impairment with good prognosis. Only rarely, they metastasize to an adjacent lymph node or produce ectopic neuroendocrine products. When found during diagnostic examination, they represent a doubt to be a malignant tumor until proven otherwise, which is often impossible without biopsy or surgical removal of the adjacent lung lobe. Hereby, we present a patient with a persistent nodular lung structure after being treated for nonspecific symptoms, cough with non purulent sputum and pain among the scapulae, for a period of one month. He had otherwise normal clinical and laboratory findings, except for a mild mixed obstructive/restrictive pattern of impairment that was shown by lung spirometry. After 8 months, he underwent lobectomy of the medial lobe of the lung with partial lymphadenectomy, since the diagnostic methods applied could not define the nature of lung nodular infiltration. Histologic examination showed a few tumorlets surrounded by the fibrous tissue with a very dense lymphocyte infiltration. We present a review of the literature and emphasize the necessity to include tumorlets with adjacent fibrosis as part of the differential diagnosis of a solitary nodular lung structure.Plućni tumorleti su malene, često višestruke nodularne proliferacije plućnih neuroendokrinih stanica te su čest slučajni nalaz kod kroničnih upalnih plućnih bolesti. Također se mogu naći u normalnom plućnom parenhimu te kao jedan dio kontinuuma poznatog kao difuzna idiopatska hiperplazija plućnih neuroendokrinih stanica. U mnogim slučajevima oni su slučajni histološki nalaz bez značenja ili kliničkih posljedica, a mogu biti i povezani s vrlo sporom progresijom opstruktivnog ili miješanog opstruktivno-restriktivnog oštećenja s dobrom prognozom. Samo rijetko metastaziraju u obližnje limfne čvorove ili stvaraju ektopične neuroendokrine produkte. Nađeni tijekom dijagnostičkog pregleda, predstavljaju sumnju na maligni tumor sve dok se ne dokaže suprotno, što je često nemoguće bez biopsije ili kirurškog odstranjenja pripadajućeg plućnog režnja. Prikazuje se bolesnik s ustrajnim čvorom unutar plućnog parenhima nakon što je tijekom mjesec dana bio liječen zbog nespecifičnih simptoma – kašlja bez gnojnog iskašljaja i boli između lopatica. Ostali su klinički i laboratorijski nalazi bili uredni osim blagog miješanog opstruktivno-restriktivnog oštećenja. Nakon 8 mjeseci odstranjen je srednji režanj pluća zajedno s dijelom limfnih čvorova, jer primijenjene dijagnostičke metode nisu mogle odrediti prirodu čvoraste infiltracije pluća. Histološki pregled je pokazao nekoliko tumorleta okruženih fibroznim tkivom uz vrlo gustu infiltraciju limfocitima. U ovom članku donosimo pregled literature te prikaz slučaja koji naglašava neophodnost uključivanja tumorleta s okolnim fibroznim tkivom u diferencijalnu dijagnozu solitarne nodularne strukture u plućima

Serumska koncentracija vitamina D u bolesnika s vulgarnom psorijazom

Introduction: Psoriasis is a chronic, inflammatory systematic disease that primarily affects the skin. Various factors influence the disease outcome and severity, among which the influence of vitamin D serum levels could potentially be important for disease pathogenesis and therapeutic strategies. Aim: To analyze vitamin D serum levels in patients with psoriasis in comparison to healthy individuals, together with markers of inflammation and disease severity. Methods: The study included patients with psoriasis that formed the case group, while the control group consisted of healthy individuals. The investigated features were demographical data, body mass index (BMI), disease severity, vitamin D serum levels, inflammatory markers, and parathyroid hormone (PTH) levels. Results: The study included 112 participants, 60 in the case group and 52 in the control group with the median age of 49 years. Physical activity was higher in the control group, while the body mass and the BMI were higher in the case group. Participants’ BMI negatively correlated to vitamin D serum levels, as well as C-reactive protein values in the control group and PTH in the case group. There was no significant difference in nicotine and alcohol consumption, sun exposure or vitamin D levels between the two groups. Conclusion: Both groups presented with vitamin D serum levels in the deficiency range. The seasons of the year and the participants’ BMI affected vitamin D status. Vitamin D levels were equally distributed between the groups without influence on disease severity.Uvod: Vulgarna psorijaza kronična je, upalna, sustavna bolest koja se primarno očituje promjenama kože. Različiti čimbenici utječu na ishod liječenja i težinu ove bolesti, a među njima se posebno izdvaja potencijalno važna uloga serumskih koncentracija vitamina D kako u patogenezi tako i kao terapijska opcija. Cilj: Analiza serumskih koncentracija vitamina D u bolesnika koji boluju od vulgarne psorijaze u usporedbi sa zdravom kontrolnom skupinom, kao i procjena težine bolesti i utjecaja upalnih markera. Metode: U istraživanje su uključeni bolesnici koji boluju od vulgarne psorijaze i kontrolna zdrava skupina ispitanika. Istraživana su obilježja kao što su osnovni demografski podaci, indeks tjelesne mase (BMI), klinički stupanj bolesti, serumske vrijednosti vitamina D, upalni parametri te vrijednosti paratireoidnog hormona (PTH). Rezultati: U istraživanje je uključeno 112 ispitanika, 60 oboljelih te 52 ispitanika u kontrolnoj skupini s medijanom dobi od 49 godina. Znatno je viša bila razina tjelesne aktivnosti u kontrolnoj skupini, dok su među oboljelima zabilježeni veća tjelesna masa i BMI. Utvrđena je negativna korelacija između serumskih vrijednosti vitamina D i BMI-ja, kao i razine C-reaktivnog proteina u kontrolnoj skupini, odnosno vrijednosti PTH-a u oboljelih. Prilikom ispitivanja utjecaja konzumacije alkohola i nikotina, izloženosti Sunčevim zrakama i serumskih vrijednosti vitamina B nije bilo znatnih razlika između skupina. Zaključak: Zabilježene su niske koncentracije vitamina D u obje skupine ispitanika. Godišnja doba i BMI utječu na razinu vitamina D. Nije uočena snižena koncentracija vitamina D u bolesnika sa psorijazom ili utjecaj na težinu bolesti

Perioralni dermatitis: još uvijek terapijski izazov

Perioral dermatitis is a common and often chronic dermatosis. In its classic form, it primarily affects women aged 15 to 45 years, but there are also variants including lupus-like and granulomatous perioral dermatitis, where granulomatous form is more common in childhood and affects mostly prepubescent boys. The etiopathogenesis of the disease remains unclear, but there is a frequent finding of prolonged use of topical products, especially corticosteroids, in the treatment of rosacea and seborrheic dermatitis, preceding the clinical manifestation of perioral dermatitis. Other causes important for the occurrence of the disease include various skin irritants, as well as other physical and hormonal factors, which all share the epidermal barrier dysfunction as an underlying main pathogenic factor. Clinical presentation of papulovesicular eruption in the perioral region with a typical narrow spared zone around the edge of the lips is characteristic. Therapeutic approach should be individually addressed, depending on the severity of clinical presentation and patient’s age, with special attention to patient’s education and continuous psychological support. In mild forms of perioral dermatitis, ‘zero therapy’ is the treatment of choice. In the initial treatment period, patients with steroid-induced perioral dermatitis should be closely followed up because the rebound phenomenon usually develops after cessation of previous topical treatment. In moderate disease, treatment includes topical metronidazole, erythromycin, and pimecrolimus, whereas in more severe cases the best validated choice is oral tetracycline in a subantimicrobial dose until complete remission is achieved. Systemic isotretinoin should be considered as a therapeutic option for patients refractory to all standard therapies.Perioralni dermatitis je česta dermatoza, nerijetko kroničnog tijeka, od koje najčešće obolijevaju žene u dobi od 15 do 45 godina. Uz klasični oblik perioralnog dermatitisa postoje još i lupoidni te granulomatozni oblik bolesti koji se najčešće javlja u dječaka u predpubertetskom razdoblju. Etiopatogeneza perioralnog dermatitisa nije u potpunosti razjašnjena, no zna se da važnu ulogu ima dugotrajna uporaba lokalnih pripravaka od kojih su najvažniji lokalni kortikosteroidi. Uz to, za nastanak bolesti važni su i razni kožni iritansi te drugi fizikalni i hormonski čimbenici koji narušavaju funkciju epidermalne barijere, poremećaj koje je osnovni patogenetski čimbenik perioralnog dermatitisa. Klinička slika je znakovita: nalazi se papulovezikulozna erupcija s tipičnom uskom pošteđenom zonom oko ruba usnica, koja je temelj za postavljanje dijagnoze bolesti. U terapiji je nužan individualni pristup koji ovisi o težini kliničke slike i dobi bolesnika, s naglaskom na podučavanju bolesnika i stalnoj psihološkoj potpori. Takozvana „nulta terapija“ je najbolji pristup u slučaju blažih oblika bolesti, pri čemu u početnom razdoblju liječenja osobitu pozornost zahtijevaju bolesnici s perioralnim dermatitisom izazvanim steroidima, s obzirom na to da se u tom razdoblju očekuje pogoršanje znakova i simptoma bolesti uzrokovano naglim prestankom primjene dotadašnjih topikalnih pripravaka. Za liječenje umjereno teških oblika bolesti dolaze u obzir lokalni metronidazol, eritromicin i pimekrolimus, dok su oralni tetraciklini lijek izbora u težim slučajevima perioralnog dermatitisa, a primjenjuju se u subantimikrobnoj dozi do potpunog povlačenja promjena na koži. Sustavno liječenje izotretinoinom je terapijski izbor u bolesnika refraktornih na sve druge standardne oblike liječenja

Perioralni dermatitis: još uvijek terapijski izazov

Perioral dermatitis is a common and often chronic dermatosis. In its classic form, it primarily affects women aged 15 to 45 years, but there are also variants including lupus-like and granulomatous perioral dermatitis, where granulomatous form is more common in childhood and affects mostly prepubescent boys. The etiopathogenesis of the disease remains unclear, but there is a frequent finding of prolonged use of topical products, especially corticosteroids, in the treatment of rosacea and seborrheic dermatitis, preceding the clinical manifestation of perioral dermatitis. Other causes important for the occurrence of the disease include various skin irritants, as well as other physical and hormonal factors, which all share the epidermal barrier dysfunction as an underlying main pathogenic factor. Clinical presentation of papulovesicular eruption in the perioral region with a typical narrow spared zone around the edge of the lips is characteristic. Therapeutic approach should be individually addressed, depending on the severity of clinical presentation and patient’s age, with special attention to patient’s education and continuous psychological support. In mild forms of perioral dermatitis, ‘zero therapy’ is the treatment of choice. In the initial treatment period, patients with steroid-induced perioral dermatitis should be closely followed up because the rebound phenomenon usually develops after cessation of previous topical treatment. In moderate disease, treatment includes topical metronidazole, erythromycin, and pimecrolimus, whereas in more severe cases the best validated choice is oral tetracycline in a subantimicrobial dose until complete remission is achieved. Systemic isotretinoin should be considered as a therapeutic option for patients refractory to all standard therapies.Perioralni dermatitis je česta dermatoza, nerijetko kroničnog tijeka, od koje najčešće obolijevaju žene u dobi od 15 do 45 godina. Uz klasični oblik perioralnog dermatitisa postoje još i lupoidni te granulomatozni oblik bolesti koji se najčešće javlja u dječaka u predpubertetskom razdoblju. Etiopatogeneza perioralnog dermatitisa nije u potpunosti razjašnjena, no zna se da važnu ulogu ima dugotrajna uporaba lokalnih pripravaka od kojih su najvažniji lokalni kortikosteroidi. Uz to, za nastanak bolesti važni su i razni kožni iritansi te drugi fizikalni i hormonski čimbenici koji narušavaju funkciju epidermalne barijere, poremećaj koje je osnovni patogenetski čimbenik perioralnog dermatitisa. Klinička slika je znakovita: nalazi se papulovezikulozna erupcija s tipičnom uskom pošteđenom zonom oko ruba usnica, koja je temelj za postavljanje dijagnoze bolesti. U terapiji je nužan individualni pristup koji ovisi o težini kliničke slike i dobi bolesnika, s naglaskom na podučavanju bolesnika i stalnoj psihološkoj potpori. Takozvana „nulta terapija“ je najbolji pristup u slučaju blažih oblika bolesti, pri čemu u početnom razdoblju liječenja osobitu pozornost zahtijevaju bolesnici s perioralnim dermatitisom izazvanim steroidima, s obzirom na to da se u tom razdoblju očekuje pogoršanje znakova i simptoma bolesti uzrokovano naglim prestankom primjene dotadašnjih topikalnih pripravaka. Za liječenje umjereno teških oblika bolesti dolaze u obzir lokalni metronidazol, eritromicin i pimekrolimus, dok su oralni tetraciklini lijek izbora u težim slučajevima perioralnog dermatitisa, a primjenjuju se u subantimikrobnoj dozi do potpunog povlačenja promjena na koži. Sustavno liječenje izotretinoinom je terapijski izbor u bolesnika refraktornih na sve druge standardne oblike liječenja

Cytological Analysis of CSF in Patients with Acute Schizophrenia

Analiza likvora jedna je od najvažnijih pretraga u dijagnostici bolesti središnjeg živčanog sustava (SŽS). Iako se analiza likvora najčešće primjenjuje u neurološkim patološkim stanjima, svoje mjesto ima i u psihijatriji. Dosadašnje studije opisuju nekoliko vrijednih specifičnih citomorfoloških fenomena u likvoru bolesnika s akutnom shizofrenijom, koji ukazuju na upalnu, odnosno imunosno posredovanu etiopatogenezu bolesti. Potrebna su dodatna i dugoročna istraživanja koja bi potvrdila i standardizirala značaj citološke analize likvora u postavljanju dijagnoze i etiopatogeneze akutne shizofrenije.Cerebrospinal fluid (CSF) analysis is one of the most important tests in the diagnosis of central nervous system (CNS) diseases. Although CSF analysis is most commonly used in neurological pathological conditions, it also has its place in psychiatry. Studies to date have described several valuable specific cytomorphological phenomena in the cerebrospinal fluid of patients with acute schizophrenia, which indicate inflammatory or immune-mediated etiopathogenesis of the disease. Additional and long-term research is needed to confirm and standardize the importance of cytological analysis of cerebrospinal fluid in the diagnosis and etiopathogenesis of acute schizophrenia

The role of the Fas/Fas ligand system in synovia-derived osteoblasts and murine model of antigen induced arthritis

Artritis potaknut antigenom je eksperimentalni mišji model reumatoidnog artritisa induciran metiliranim goveđim serumskim albuminom. Jedna od glavnih karakteristika upalnog zglobnog zbivanja je sinovijalna hiperplazija, pri čemu hiperplastična sinovija sadrži mezenhimne prethodnike čija je diferencijacija u osteoblaste, hondroblaste ili adipocite poremećena. Kako se zna da Fas može inhibirati diferencijaciju osteoblasta podrijetlom iz koštane srži, cilj je ove studije bio pokazati izažavaju li osteoblasti sinovijalnih mezenhimnih stanica uzgojenih in vitro receptor Fas, opisati ulogu receptora Fas u njihovoj apoptozi i diferencijaciji, te razjasniti in vivo ulogu nedostatnosti receptora Fas u razvoju artritisa potaknutog antigenom. Osteoblasti sinovijalnog podrijetla slabo izražavaju receptor Fas, čija je aktivacija in vitro povećala broj apoptotičnih nezrelih osteoblasta, no taj je broj bio manji od udjela osteoblasta koji su izražavali Fas. Dodavanje protutijela anti-Fas nije potaklo apoptozu u zrelih osteoblasta. Usprkos ograničenom apoptotičnom djelovanju, aktivacija receptora Fas in vitro je značajno smanjila diferencijaciju osteoblasta sinovijalnoga podrijetla. Za procjenu in vivo učinka nedostatnosti receptora Fas koristila sam mišji model artritisa potaknutog antigenom, koji sam izazvala u miševa divljega tipa i miševa s izbačenim genom za receptor Fas (Fas –/–). Zglobnu upalu izazvala sam injekcijom metiliranog goveđeg serumskog albumina u životinja prethodno hiperimuniziranih istim antigenom, a potom zglobne promjene uspoređivala s kontrolnim miševima injiciranim fiziološkom otopinom puferiranom fosfatima, i to četrnaest dana nakon intraartikularne injekcije. Artritis je u miševa divljega tipa izazvao značajno povećanje promjera koljenih zglobova u usporedbi s kontrolnim miševima, a to je povećanje izostalo u miševa Fas –/–. Histološka procjena pokazala je znatno upalno oštećenje u miševa divljeg tipa kojima je potaknut artritis, koje je također bilo puno slabijeg intenziteta u miševa Fas –/–. Histomorfometrijska analiza jukstaartikularnih metafiza pokazala je smanjenje volumena trabekularne kosti, broja i širine koštanih gredica te povećanje odvojenosti koštanih gredica u miševa divljega tipa s artritisom u odnosu na kontrolnu skupinu miševa. Sličan je bio i nalaz mikro-kompjutorizirane tomografije koji je potvrdio smanjenje volumena trabekularne kosti i broja koštanih gredica te povećanje razdvojenosti koštanih gredica u odnosu na kontrole. Navedene promjene nisu opažene u Fas –/– miševa s artritisom, čiji su koštani parametri u skupini miševa s artritisom bili slični kontrolnoj skupini miševa. Artritis potaknut antigenom pojačao je osteoblastnu diferencijaciju sinovijalnih mezenhimnih prethodnika, te mezenhimnih prethodnika koštane srži u miševa divljega tipa, a u miševa Fas –/– je taj učinak opažen samo u mezenhimnih prethodnika koštane srži. Temeljni zaključak ovoga istraživanja je da sustav Fas/ligand Fas ima ulogu u nadzoru nad brojem i diferencijacijacijom osteoblasta sinovijalnog podrijetla, pri čemu u manjoj mjeri time što potiče njihovu apoptozu, a značajnije inhibicijom osteoblastogeneze. Nedostatnost receptora Fas ima zaštitni učinak na lokalni i jukstaartikularni gubitak kosti u artritisu potaknutom antigenom.Antigen induced arthritis is a murine experimental model of rheumatoid arthritis induced by methylated bovine serum albumin. One of the main characteristics of joint inflammation is synovial hyperplasia, whereas hyperplastic synovium in arthritis contains mesenchymal progenitors with reduced ability to differentiate into osteoblasts, chondroblasts or adipocytes. Since Fas has been shown to inhibit osteoblast differentiation, the purpose of this study was to determine whether synovia-derived osteoblasts express Fas in vitro; describe the role of Fas in apoptosis and differentiation of synovia-derived osteoblasts in vitro; as well as elucidate the in vivo role of Fas deficiency in antigen induced arthritis. Fas receptor was weakly expressed on synovia-derived osteoblasts. Fas activation increased the number of apoptotic immature osteoblasts in vitro but the number was smaller than the proportion of Fas expressing osteoblasts. Addition of activating anti-Fas antibody did not induce apoptosis of mature osteoblasts. Despite the limited induction of apoptosis, Fas activation significantly inhibited differention od synovia-derived osteoblasts in vitro. In order to assess the in vivo effect of Fas deficiency, I used the experimental model of antigen induced arthritis in wild-type mice and mice knocked-out for Fas gene (Fas –/–). Arthritis was induced by intraarticular injection of methylated bovine albumine into the knees of animals pre-immunized by the same antigen. The changes of knee joints were compared with control mice injected by phosphate buffered saline, 14 days after intraarticular injection. Knee diameters were significantly increased in wild-type mice with induced arthritis compared to their controls, while this increase was not significant in Fas –/– mice. Histology revealed pronounced inflammatory parameters in joints of wild-type mice with arthritis, while the inflammation in arthritis-induced Fas –/– mice was significantly less developed. Histomorphometric analysis showed a decreased trabecular bone volume, trabecular number and thickness, as well as increased trabecular separation in wild-type mice with arthritis compared to controls. Additionally, micro-computerized tomography analysis showed that wild-type mice with arthritis had a decreased trabecular bone volume and trabecular number, as well as increased trabecular separation compared to controls. Described changes in trabecular bone were not found in Fas –/– mice with arthritis, whose bone parameters were similar to those of controls. In vitro osteoblast differentiation from both synovial mesenchymal cells and bone marrow cells was increased in wild-type mice with induced arthritis, whereas only osteoblast differentiation from bone marrow mesenchymal stromal cells was increased in arthritic Fas –/– mice. The main conclusion of this study is that the Fas/FasL system regulates the number and differentiation od synovia-derived osteoblasts, which is only partially related to the induction of apoptotic cell death but dominantly to the inhibition of osteoblastogenesis. Fas deficiency has a protective role in local and juxtaarticular bone loss in antigen induced arthritis