Human bone matrix is known to contain a battery of polypeptide growth factors. Since dentin is a mineralized tissue similar to bone in composition and perhaps in formation, human dentin was assayed for the presence of similar growth factors. Root dentin proteins were extracted by demineralization in 4 M guanidine hydrochloride (Gu) and 30 mM Tris (pH 7.4) containing 20% EDTA and proteinase inhibitors. Gu-EDTA extracts were desalted and used for the following assays: (1) bone cell proliferation in chick calvarial cell mitogenic assay using the incorporation of [3H]thymidine into TCA-insoluble material; (2) osteocalcin by radioimmunoassay (RIA); (3) insulin-like growth factor I (IGF-I) by RIA; (4) skeletal growth factor/insulinlike growth factor II (SGF/IGF-II) by radioreceptor assay; and (5) transforming growth factor beta (TGF-beta) by bioassay. Gu-EDTA extracts stimulated bone cell proliferation. At 10 micrograms/ml, dentin proteins increased the incorporation of [3H]thymidine by calvarial cells to 320% of that by BSA-treated control cells. Consistent with the presence of mitogenic activity, growth factors were found in dentin in the following concentrations (ng/micrograms Gu-EDTA protein): (1) IGF-I, 0.06; (2) SGF/IGF-II, 0.52; and (3) TGF-beta, 0.017. All three growth factors were present in concentrations lower than that found in human bone. Osteocalcin was detected at a concentration of 3.0 mg/g Gu-EDTA protein, also much lower than that in bone.
The Blueprint for Advancing High-Value Maternity Care Through Physiologic Childbearing charts an efficient pathway to a maternity care system that reliably enables all women and newborns to experience healthy physiologic processes around the time of birth, to the extent possible given their health needs and informed preferences. The authors are members of a multistakeholder, multidisciplinary National Advisory Council that collaborated to develop this document. This approach preventively addresses troubling trends in maternal and newborn outcomes and persistent racial and other disparities by mobilizing innate capacities for healthy childbearing processes and limiting use of consequential interventions. It provides more appropriate care to healthier, lower-risk women and newborns who often receive more specialized care, though such care may not be needed and may cause unintended harm. It also offers opportunities to improve the care, experience and outcomes of women with health challenges by fostering healthy perinatal physiologic processes whenever safely possible.
Beta transforming growth factor (TGF beta) has multiple in vitro biological effects including stimulation or inhibition of proliferation of specific cell types. A second major form of TGF beta, TGF beta-2, has recently been isolated from porcine platelets, from bovine bone matrix, and from several other sources. The two forms of TGF beta are biologically equipotent with the exception that TGF beta-2 was much less active than TGF beta-1 for inhibition of proliferation of a rat pleuripotent hematopoietic stem cell line. During the purification of beta TGF from bone, we obtained two fraction pools that differed in their ability to inhibit 3H-thymidine incorporation into aortic endothelial cells (AEC). We therefore compared highly purified TGF beta-1 and TGF beta-2 isolated from porcine platelets for inhibition of DNA synthesis in mink lung epithelial cells (MvILu), and in AEC, and for stimulation of 3H-thymidine incorporation in calvarial bone cells (CBC) in 3 experiments. TGF beta-1 and TGF beta-2 inhibited cell proliferation in MvILu with no significant differences in the ED50 (31 +/- 8 pg/ml vs 23 +/- 7). TGF beta-2 was much less potent than TGF beta-1 in inhibiting DNA synthesis in AEC (6310 +/- 985 pg/ml vs 101 +/- 34). The reduced specific activity of TGF beta-2 was also observed in adrenal capillary endothelial cells. Both beta-1 and beta-2 stimulated proliferation of CBC (ED50 26 +/- 2 pg/ml vs 10 +/- 4). We also examined the specificity of the MvILu and AEC inhibition assays. Epidermal growth factor (EGF), platelet derived growth factor (PDGF), acidic and basic fibroblast growth factors (FGF), skeletal growth factor (SGF)/insulin-like growth factor-II (IGF-II), and insulin-like growth factor-I (IGF-I) did not inhibit DNA synthesis in either assay system. However, when the growth factors were added to maximal inhibiting concentrations of TGF beta-1, both acidic and basic FGF significantly reduced TGF beta-1 inhibition in AEC. We conclude that (1) inhibition of DNA synthesis in endothelial cells is relatively specific for TGF beta-1, (2) inhibition of DNA synthesis in MvILu is a sensitive and specific assay for generic TGF beta activity but does not distinguish beta-1 from beta-2, (3) the relative inhibition of DNA synthesis in MvILu and AEC may provide a means to quantitatively estimate TGF beta-1 and TGF beta-2, and (4) both TGF beta-1 and TGF beta-2 are potent mitogens for chicken embryonic calvarial bone cells.
Recently, we reported a direct effect of androgens on murine and human bone cells to stimulate bone cell proliferation and differentiation. To test whether this effect of androgenic steroids might be mediated by growth factors, we measured relative concentrations of insulin-like growth factor-I and -II (IGF-I and IGF-II) and transforming growth factor-beta (TGF beta) in the conditioned medium from androgen-treated murine calvarial cell cultures. Only the concentration of TGF beta was increased. Consistent with the increased secretion of TGF beta in the mouse calvarial cell system, we observed an increased expression of TGF beta mRNA in a normal human osteoblastic cell system. We also determined whether androgens alter the response to growth factors. We found that dihydrotestosterone (DHT) treatment enhanced the mitogenic effects of fibroblast growth factor (FGF) and IGF-II but not those of IGF-I. The enhanced effect of FGF and IGF-II after DHT pretreatment was not affected by addition of TGF beta-blocking antibodies or by changing the culture medium. This indicated that in addition to increased release of TGF beta, another mechanism might be involved in the action of DHT on human and murine bone cells. Thus, we investigated the binding of human IGF-II to human osteoblastic cells and observed an increase in IGF-II binding after DHT treatment. Our results are consistent with a mechanism of action of androgens on bone cells that involves the induction of TGF beta and, in addition, may sensitize the cells to show an enhanced response to FGF and IGF-II, possibly by changing the receptor binding of mitogenic growth factors.
Despite areas of excellence, US perinatal care outcomes lag behind most developed countries. In addition, a shortage and maldistribution of health care providers exists. The American College of Nurse‐Midwives and the American College of Obstetricians and Gynecologists (ACOG) partnered to obtain funding to develop interprofessional education modules and other learning activities for midwifery students and obstetrics and gynecology residents in 4 demonstration sites. The multidisciplinary 2016 ACOG document Collaboration in Practice: Implementing Team‐Based Care was adopted as a framework. Core competencies of values and ethics, roles and responsibilities, interprofessional communication, and teams and teamwork developed by the Interprofessional Education Collaborative were used to guide the work. Seven modules have been developed including guiding principles, patient‐centered care, role clarification, collaborative practice, history and culture, care transition, and difficult conversations. Learners participate in laboratory and simulation activities and work together in clinical care settings. Stakeholder experiences as well as barriers to implementation are discussed. Learning materials and activity descriptions are open resourced and shared on a project website for use by programs interested in implementing an interprofessional curriculum. Ongoing formal evaluation including pilot testing of a program evaluation method is described.
After completion of this article, the reader will be able to describe the condition idiopathic juvenile osteoporosis, compare the clinical features of this condition to other similar conditions, outline the diagnostic workup of a child with this condition, and list the potential therapeutic options for a patient with idiopathic juvenile osteoporosis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.