The osteopetrotic mutation toothless (tl) is a loss-of-function frameshift mutation in the rat Csf1 gene: Evidence of a crucial role for CSF-1 in osteoclastogenesis and endochondral ossification

The toothless (tl) mutation in the rat is a naturally occurring, autosomal recessive mutation resulting in a profound deficiency of bone-resorbing osteoclasts and peritoneal macrophages. The failure to resorb bone produces severe, unrelenting osteopetrosis, with a highly sclerotic skeleton, lack of marrow spaces, failure of tooth eruption, and other pathologies. Injections of CSF-1 improve some, but not all, of these. In this report we have used polymorphism mapping, sequencing, and expression studies to identify the genetic lesion in the tl rat. We found a 10-base insertion near the beginning of the open reading of the Csf1 gene that yields a truncated, nonfunctional protein and an early stop codon, thus rendering the tl rat CSF-1null. All mutants were homozygous for the mutation and all carriers were heterozygous. No CSF-1 transcripts were identified in rat mRNA that would avoid the mutation via alternative splicing. The biology and actions of CSF-1 have been elucidated by many studies that use another naturally occurring mutation, the op mouse, in which a single base insertion also disrupts the reading frame. The op mouse has milder osteoclastopenia and osteopetrosis than the tl rat and recovers spontaneously over the first few months of life. Thus, the tl rat provides a second model in which the functions of CSF-1 can be studied. Understanding the similarities and differences in the phenotypes of these two models will be important to advancing our knowledge of the many actions of CSF-1

Articular chondrocytes produce factors that inhibit maturation of sternal chondrocytes in serum-free agarose cultures: A TGF-ß independent process

Under normal conditions, articular chondrocytes persist throughout postnatal life, whereas \u27transient\u27 chondrocytes, which constitute the bulk of prenatal and early postnatal cartilaginous skeleton, undergo maturation, hypertrophy, and replacement by bone cells. The mechanisms regulating the markedly different behavior and fate of articular and transient chondrocytes are largely unclear. In the present study, we asked whether articular chondrocytes possess dominant antimaturation properties which may subtend their ability to persist throughout life. Adult chicken articular chondrocytes and transient maturing chondrocytes from the core region of day 17 chick embryo cephalic sternum were cultured or cocultured in serum-free agarose conditions. When the sternal cells were grown by themselves, they quickly developed into hypertrophic type X collagen-synthesizing cells; however, when they were cocultured with as few as 10% articular chondrocytes or fed with articular chondrocyte-conditioned medium, their maturation was markedly impaired, as revealed by a sharp drop in type X collagen synthesis. A similar, albeit less potent, antimaturation activity characterized resting and proliferating immature chondrocytes isolated from other regions of embryonic sternum. Transforming growth factor-ß2 (TGF-ß2) was previously suggested to be an inhibitor of chondrocyte maturation. We found, however, that treatment with a neutralizing antiserum to TGF-ß did not counteract the inhibition of maturation in cocultures of articular and maturing core sternal chondrocytes. Indeed, articular chondrocytes produced and accumulated relatively low levels of TGF-ß in their culture medium, about 15 ng/ml/48 h, of which over 90% was latent; surprisingly, maturing sternal core chondrocytes accumulated over 10-fold more TGF-ß in the medium, about 150 ng/ml/48 h, of which over 20% was endogenously active. These results indicate that articular chondrocytes do possess dominant antimaturation properties which appear to be TGF-ß independent. The TGF-ßs may thus have a more prominent role in the terminal phases of chondrocyte maturation, as indicated by their abundance and greater activity in hypertrophic chondrocytes

TISSUE: A Pre-Matriculation Anatomical Sciences Program Developed by Medical Students for Incoming Medical Students

The TISSUE (Teaching Introductory Study Skills Utilizing Experience) program was created to provide exposure to the anatomical sciences for students who had not taken courses in anatomy and/or histology, had received an undergraduate degree in a non-science concentration, and/or who had not been involved in an academic setting for some time. This program was developed for incoming medical students by current medical students. The main goal of TISSUE was to mitigate the perceived academic, emotional, and personal stress of the incoming first year medical students. The program touched upon academics, study strategies, time management, and student wellness and was offered to the incoming Philadelphia College of Osteopathic Medicine Class of 2021 Doctor of Osteopathic Medicine students, with the option to participate in an in-person or online cohort. Outcomes assessment was measured by surveying the students post-course in reference to stated learning outcomes related to both anatomical sciences and transitioning to medical school. Supplemental research projects will investigate the effect of participating in the TISSUE course on perceived academic and transitional stress in first year medical students. This research will contribute to a growing body of data collected by the administration and mental health counselors to better tailor mental health counseling opportunities, student support groups, and a curriculum that supports the health and happiness of medical students

Transforming growth factor-ß modulation of glycosaminoglycan production by mesenchymal cells of the developing murine secondary palate

Development of the mammalian secondary palate requires proper production of the extracellular matrix, particularly glycosaminoglycans (GAGs) and collagen. Endogenous factors that regulate the metabolism of these molecules are largely undefined. A candidate for a locally derived molecule would be transforming growth factor ß1(TGFß1) by virtue of its potency as a modulator of extracellular matrix metabolism by several cell lines. We have thus attempted to assign a regulatory role for TGFß1 in modulation of GAG production and degradation by mesenchymal cells of the murine embryonic palate (MEPM). Treatment with TGFß1 or TGFß2, but not IGF-II, resulted in a stimulation of total GAG synthesis. Furthermore, cells treated with bothTGFß1 and TGFa showed a synergistic increase in GAG synthesis if pretreated with TGFß1 but not TGFa. Simultaneous stimulation with TGFß1 and TGFß2 did not elicit a synergistic response. These studies demonstrate the ability of TGFß, synthesized by embryonic palatal cells, to specifically stimulate GAG synthesis by MEPM cells. Other growth factors present in the developing craniofacial region may also modulate TGFß-induced GAG synthesis, a biosynthetic process critical to normal development of the embryonic palate

Activation of TGFß2 accompanies chondrocyte maturation and is metalloprotease-mediated

No abstract available

A Blended Learning Approach in a Pre-Matriculation Course for Incoming Medical Students

Technology in medical education is best used to efficiently deliver content of academic courses. TISSUE (Teaching Introductory Study Skills Utilizing Experience), a pre-matriculation course for incoming first-year medical students, utilized a blended online/in-person course format to increase outreach and remove time, financial, and distance barriers to learning. The TISSUE program was created to provide exposure to the anatomical sciences for students who had not taken courses in anatomy and/or histology. Second year medical student (OMS 2) facilitators of the course engaged in-class students on topics such as academics, study strategies, time management, and student wellness. To maximize the number of students able to participate in the TISSUE course, BlueJeans, a webinar platform, was utilized. The webinar platform incorporated collaboration tools such as the screen-share function, chat function, and ability to record lectures for viewing at a later date. The online component allowed students who were unable to participate in the in-person course to actively collaborate with the in-person class and facilitators. Flexibility was the main advantage allowing students from all over the country to access content at a time that is convenient for them. Employing a blended learning format in the TISSUE program illustrated one of the many ways that medical education is utilizing new technology to assist students with their transition to medical school

The Sebaceous Gland - Friend or Foe?

Introduction: Sebaceous glands are sebum-secreting components of pilosebaceous units, that play a key role in eccrine emulsification, the impermeability of skin and hair, cytokine, chemokine, interleukin, pheromone, and fatty acid synthesis, acid mantle formation, and hormone production. Although the sebaceous gland has been heavily investigated, many advances in the physiology and pathology of the sebaceous gland have since been identified. Objective: The primary objective of this publication was to perform an updated literature review of the embryology, evolution, structure and function, and pathophysiological disorders associated with the sebaceous gland. Methods: We performed a literature search using PubMed database with keywords sebaceous glands, sebocytes, sebaceous adenoma, sebaceous carcinoma, sebaceous gland hyperplasia, androgenic alopecia, acne vulgaris, and nevus sebaceus, among others. Results: New criteria suggests all patients presenting with sebaceous neoplasms should be screened for Muir-Torr Syndrome (MTS). Germline MMR genetic testing is recommended if colon or endometrial cancers are not present. New research demonstrates that the risk of secondary benign growths of nevus sebaceus remains high, but risk of malignancy is relatively low, and thus surgical excision is not always recommended. In recent years, platelet-rich plasma (PRP) has emerged as a potential new treatment for androgenic alopecia; however, further studies are required to prove PRP efficacious in the treatment of AGA. The Janus kinase/signal transducer (JAK/STAT) signaling pathway, which has been implicated in multiple inflammatory skin conditions, may play a role in the pathogenesis of acne vulgaris. mRNA expression of JAK1 and JAK3 in skin biopsies from acne patients were significantly elevated in comparison to controls (p Conclusions: Sebaceous glands are notable for androgen-regulated; sebum secretion into the infundibular portion of the hair follicle; regulation of cutaneous steroidogenesis, and local androgen synthesis in the pilosebaceous unit and epidermal keratinocytes. They play a critical role in fetal production of vernix caseosa, a lipid-rich substance composed of shed periderm cells and sebum secretions forming around 21 weeks gestation; exhibition of pro- and antiinflammatory properties; synthesis of antimicrobial peptides; neuropeptides, and cytokines; and delivery of antioxidants to the skin. Abnormal sebaceous gland activity has been implicated in a number of medical conditions, including steacystoma simplex and multiplex, sebaceous gland hyperplasia, sebaceoma, sebaceous adenoma, sebaceous carcinoma, nevus sebaceus, and folliculosebaceous cystic hamartoma, acne vulgaris, seborrheic dermatitis, and androgenic alopecia

Immunodetection of the transforming growth factors ß1 and ß2 in the developing murine palate

The expression of some members of the TGFß family of genes in embryonic craniofacial tissue suggests a functional role for these molecules in orofacial development. In other systems, TGFß1 and TGFß2 have been shown to regulate cell proliferation and extracellular matrix metabolism, processes critical to normal development of the secondary palate. We have thus determined the amount and tissue distribution of both TGFß1 and TGFß2 in embryonic palatal tissue. Cellular extracts of murine embryonic palatal tissue from days 12, 13 and 14 of gestation were assayed for the presence of TGFß1 and TGFß2 by immunoprecipitation. Physiological levels, ranging from 0.05-20 ng/µg protein, of both growth factors were detected in all tissues examined. Immunostaining with antibodies directed against either TGFß1 or TGFß2 demonstrated the presence of these growth factors in palatal epithelium and mesenchyme early during palatal development (gestational day [GD] 12) a period characterized by tissue growth. On GDs 13 and 14, characterized by palate epithelial differentiation, immunostaining for both growth factors predominated in epithelial tissue. Immunostaining for TGFß1 and TGFß2 was also intense in mesenchyme surrounding tooth germs and in perichondrium. Chondrocytes and cartilage extracellular matrix did not stain for either TGFß1 or ß2. Combined with existing evidence for the presence of functional receptors for the transforming growth factor-ßs in the developing palate, these results provide rationale for studies designed to clarify a specific role for these signalling molecules in palate epithelial differentiation and/or epithelial-mesenchymal interactions