Differential Expression of Cadherin-2 and Cadherin-4 in the Developing and Adult Zebrafish Visual System

Cadherins are homophilic cell adhesion molecules that control development of a variety of tissues and maintenance of adult structures. Although cadherins have been implicated in the development of the brain, including the visual system, in several vertebrate species, little is known of their role in zebrafish. In this study, we examined distribution of cadherin-2 (Cdh2, N-cadherin) in the visual system of developing and adult zebrafish using both immunocytochemical and in situ hybridization methods, and we compared Cdh2 distribution to that of the previously reported and closely related cadherin-4 (Cdh4, R-cadherin). As in other vertebrates, in zebrafish embryos Cdh2 was widely expressed in the early nervous system, but its expression became more restricted as development proceeded. Cdh4 was not detectable until later in development, at about the time when the first ganglion cells are generated. Cdh2 and Cdh4 were expressed in distinct regions of developing visual structures, including the lens. We hypothesize that the differential expression of these two cadherins in developing zebrafish visual structures reflects functionally different roles in the development of the vertebrate visual system

Development, Disease, and Regeneration of Tissues in the Dental-Craniofacial Complex

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Proteoglycan 4: A dynamic regulator of skeletogenesis and parathyroid hormone skeletal anabolism

Proteoglycan 4 ( Prg4 ), known for its lubricating and protective actions in joints, is a strong candidate regulator of skeletal homeostasis and parathyroid hormone (PTH) anabolism. Prg4 is a PTH‐responsive gene in bone and liver. Prg4 null mutant mice were used to investigate the impact of proteoglycan 4 on skeletal development, remodeling, and PTH anabolic actions. Young Prg4 mutant and wild‐type mice were administered intermittent PTH(1–34) or vehicle daily from 4 to 21 days. Young Prg4 mutant mice had decreased growth plate hypertrophic zones, trabecular bone, and serum bone formation markers versus wild‐type mice, but responded with a similar anabolic response to PTH. Adult Prg4 mutant and wild‐type mice were administered intermittent PTH(1–34) or vehicle daily from 16 to 22 weeks. Adult Prg4 mutant mice had decreased trabecular and cortical bone, and blunted PTH‐mediated increases in bone mass. Joint range of motion and animal mobility were lower in adult Prg4 mutant versus wild‐type mice. Adult Prg4 mutant mice had decreased marrow and liver fibroblast growth factor 2 (FGF‐2) mRNA and reduced serum FGF‐2, which were normalized by PTH. A single dose of PTH decreased the PTH/PTHrP receptor (PPR), and increased Prg4 and FGF‐2 to a similar extent in liver and bone. Proteoglycan 4 supports endochondral bone formation and the attainment of peak trabecular bone mass, and appears to support skeletal homeostasis indirectly by protecting joint function. Bone‐ and liver‐derived FGF‐2 likely regulate proteoglycan 4 actions supporting trabeculae formation. Blunted PTH anabolic responses in adult Prg4 mutant mice are associated with altered biomechanical impact secondary to joint failure. © 2012 American Society for Bone and Mineral ResearchPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/89450/1/508_ftp.pd

Impact of proteoglycan‐4 and parathyroid hormone on articular cartilage

Proteoglycan‐4 ( Prg4 ) protects synovial joints from arthropathic changes by mechanisms that are incompletely understood. Parathyroid hormone (PTH), known for its anabolic actions in bone, increases Prg4 expression and has been reported to inhibit articular cartilage degeneration in arthropathic joints. To investigate the effect of Prg4 and PTH on articular cartilage, 16‐week‐old Prg4 mutant and wild‐type mice were treated with intermittent PTH (1–34) or vehicle control daily for six weeks. Analyses included histology of the knee joint, micro‐CT of the distal femur, and serum biochemical analysis of type II collagen fragments (CTX‐II). Compared to wild‐type littermates, Prg4 mutant mice had an acellular layer of material lining the surfaces of the articular cartilage and menisci, increased articular cartilage degradation, increased serum CTX‐II concentrations, decreased articular chondrocyte apoptosis, increased synovium SDF‐1 expression, and irregularly contoured subchondral bone. PTH‐treated Prg4 mutant mice developed a secondary deposit overlaying the acellular layer of material lining the joint surfaces, but PTH‐treatment did not alter signs of articular cartilage degeneration in Prg4 mutant mice. The increased joint SDF‐1 levels and irregular subchondral bone found in Prg4 mutant mice introduce novel candidate mechanisms by which Prg4 protects articular cartilage. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 183–190, 2013Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94686/1/22207_ftp.pd

The transmembrane inner ear (tmie) gene contributes to vestibular and lateral line development and function in the zebrafish ( Danio rerio )

The inner ear is a complex organ containing sensory tissue, including hair cells, the development of which is not well understood. Our long-term goal is to discover genes critical for the correct formation and function of the inner ear and its sensory tissue. A novel gene, transmembrane inner ear ( Tmie ), was found to cause hearing-related disorders when defective in mice and humans. A homologous tmie gene in zebrafish was cloned and its expression characterized between 24 and 51 hours post-fertilization. Embryos injected with morpholinos (MO) directed against tmie exhibited circling swimming behavior (∼37%), phenocopying mice with Tmie mutations; semicircular canal formation was disrupted, hair cell numbers were reduced, and maturation of electrically active lateral line neuromasts was delayed. As in the mouse, tmie appears to be required for inner ear development and function in the zebrafish and for hair cell maturation in the vestibular and lateral line systems as well. Developmental Dynamics 237:941–952, 2008. © 2008 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58082/1/21486_ftp.pd

Zoledronic acid inhibits macrophage SOCS3 expression and enhances cytokine production

Suppressor of cytokine signaling‐3 (SOCS3) has multiple functions including inhibition of Janus kinase (Jak) activity, regulation of protein degradation, and suppression of cytokine signaling. SOCS3 modulates macrophage response to cytokines such as IL‐6 and leptin that are systemically induced in obesity. Obesity is a suspected risk factor for SOCS3‐related pathology such as rheumatoid arthritis and Crohn's disease as well as zoledronic acid (ZA)‐induced osteonecrosis of the jaw (ONJ). Thus, understanding the ability of bisphosphonates to modulate SOCS3 is necessary to qualify their contribution to these disorders. ONJ occurs in up to 10% of patients using intravenous bisphosphonates and has an unknown pathogenesis that may be linked to decreased bone turnover, altered vascularity, bacterial invasion, and compromised wound healing. Given the increased risk of ONJ with obesity and importance of macrophages in wound healing, we hypothesized that amino‐bisphosphonates could contribute to the pathogenesis of ONJ by regulating macrophage responses to cytokines such as leptin and IL‐6. We report that ZA is a novel inhibitor of SOCS3 in primary macrophages and human ONJ biopsy specimens. Inhibition of SOCS3 by ZA resulted in significant increases in IL‐6 production. SOCS3 transcription is regulated by nuclear accumulation of phosphorylated‐Stat3 (P‐Stat3). We found that ZA decreased phosphorylation of Stat3 in a mevalonate‐pathway dependent manner. However, restoration of P‐Stat3 was not sufficient to correct SOCS3 inhibition. We propose that disruption of macrophage SOCS3 expression by amino‐bisphosphonates such as ZA may be a novel contributor to inflammatory phenotypes in obesity and the pathogenesis of ONJ. J. Cell. Biochem. 112: 3364–3372, 2011. © 2011 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87102/1/23267_ftp.pd

Analisis Konstruksi Alat Tangkap Cantrang di Pelabuhan Perikanan Pantai (PPP) Mayangan Probolinggo Jawa Timur.

Penelitian ini dilaksanakan pada bulan Januari- April 2015 di Pelabuhan Perikanan Pantai (PPP) Mayangan, Probolinggo-Jawa Timur. Tujuan dilaksanakannya penelitian ini adalah menganalisis perbedaan tiga sampel konstruksi alat tangkap cantrang di PPP Mayangan Probolinggo dan untuk mengetahui konstruksi daya hidrostatis yang bekerja pada alat tangkap cantrang. Metode yang digunakan dalam penelitian ini adalah metode deskriptif komparatif yaitu dengan teknik pengambilan data primer dan data sekunder. Pengumpulan data dilakukan dengan cara mengukur ketiga alat tangkap secara langsung. Bagian-bagian yang diukur yaitu sayap, mulut, badan, dan kantong. Pada bagian sayap yang diukur adalah pelampung, webbing (jaring), tali-temali dan pemberat. Bagian mulut yang diukur pelampung. Bagian badan yang diukur yaitu ukuran mata, jumlah mata, panjang jaring badan. Bagian kantong yang diukur yaitu ukuran mata jaring, jumlah mata, dan panjang kantong. Analisis data yang digunakan pada penelitian ini yaitu analisis konstruksi meliputi daya apung (bouyancy) dan daya tenggelam (singking force) pada saat alat tangkap dioperasikan. Analisis daya-daya hidrostatis dari ketiga sampel kontruksi pada bagian sayap alat tangkap cantrang maka hasil yang didapatkan dari masing-masing alat tangkap dengan kapal yang berbeda yaitu: Pada alat tangkap KM. Sang Engon 3. memilki daya apung 9,67 kgf dan daya pemberat 21,82 kg. KM Mandiri memilki daya apung 11,86 kgf dan daya pemberat 16,20. KM. Angkasa Jaya memilki daya apung 10,95 kgf dan daya pemberat 21,60. Pada bagian mulut daya apung pelampung yaitu 2,8 kgf dengan berat pelampung 6,2 kgf, 4,1 kgf dan 5,5 kg. Jumlah mata horizontal pada bagian badan alat tangkap cantrang KM. Sang Engon 3 1040 , KM Mandiri 1250 dan KM angkasa Jaya 1873 dan Jumlah Mata vertikal KM.Sang Engon 1177, KM Mandiri 825 dan KM.Angkasa Jaya 935. Pada Bagian kantong ukuran benang pada ketiga alat tangkap memilki ukuran benang yang sama yaitu PE.380 D/12 ukuran mata jaring pada alat tangkap cantrang KM. Mandiri yaitu 20 mm, KM Sang Engon.3 yaitu 23 mm dan KM.Angkasa Jaya yaitu 10 mm. Pada KM.Sang Engon.3 jumlah mata horizontal 180, vertikal 210, KM. Mandiri jumlah mata horizontal 267, vertikal 250, KM. Angkasa Jaya jumlah mata horizontal 288, vertikal 155. Kantong memilki mesh size yang paling kecil daripada bagian yang lain karena berfungsi untuk menampung ikan-ikan hasil tangkapan. Tali selambar yang digunakan memilki diameter 24 mm dengan panjang 1300 m. Pada ketiga alat tangkap yang diteliti KM. Sang Engon.3, KM. Mandiri, dan KM.Angkasa Jaya memilki ukuran yang berbeda pada setiap bagiannya. Panjang pada bagian sayap secara berurutan yaitu 26 m,24m dan 30m . panjang kantong 2,3 m, 3,6 m dan 3,2 m. Panjang tali selambar 1300 m, 1300 m, dan 1250 m. Untuk bagian Badan pada KM.Sang Engon.3 ukuran mata 44 mm, KM.Mandiri dan KM. Angkasa Jaya 42 mm. Jumlah Mata vertikal dan horizontal KM. Sang Engon.3 1040x1177, KM. Mandiri 1250x825, KM.Angkasa Jaya 1873 x 935. Pada ketiga sampel kapal yang digunakan, alat tangkap pada KM.Sang Engon.3 yang memilki ukuran yang baik. Perlu dilakukan penelitian lanjut tentang hasil tangkapan dan efektifitas dari kontruksi alat tangkap agar hasil tangkapan yang didapatkan bisa optimal

Proteoglycan-4: A Dynamic Regulator of Parathyroid Hormone Biologic Actions.

Intermittent parathyroid hormone (PTH) (1-34) is the only anabolic agent currently approved for the treatment of osteoporosis in the U.S. PTH (1-34) is under clinical investigations as a local bone regenerative therapy and as a potential stem cell therapy following bone marrow transplants. While PTH has known actions increasing bone mass and supporting the expansion of hematopoietic progenitor cells (HPCs), the mechanisms mediating such actions are poorly understood. Most recently it was reported that intermittent PTH protects articular cartilage in degenerating joints. Proteoglycan 4 (Prg4), a novel PTH-responsive gene, was investigated as a potential mediator of PTH biologic actions. Prg4 protein product actions have been implicated in articular joint protection, HPC expansion, and megakaryopoiesis. Loss-of-function mutations in PRG4 result in camptodactyly-arthropathy-coxa vara-pericarditis syndrome, which is characterized by precocious joint failure and osteopenia. The overall hypothesis that proteoglycan 4 mediates PTH actions in hematopoiesis, skeletal anabolism, and degenerating joints was investigated using in vitro and in vivo strategies with Prg4 null mice. The investigation of proteoglycan 4 effects on hematopoiesis in adult Prg4 mutant mice revealed that proteoglycan 4 is an immunomodulatory factor regulating physiologic immune cell populations and PTH actions increasing HPCs. SDF-1 was identified as a strong candidate regulator of proteoglycan 4 actions on hematopoiesis. Skeletogenesis studies demonstrated that proteoglycan 4 supports endochondral bone formation and the attainment of peak trabecular bone mass in the developing skeleton. In the mature remodeling skeleton proteoglycan 4 appears to indirectly support skeletal homeostasis and PTH anabolic actions by protecting joint function. Findings that PTH regulated gene expression similarly in bone and liver highlight the liver as a potential mediator of PTH biologic actions. The joint investigation identified increased joint SDF-1 levels as a novel candidate mechanism mediating articular cartilage degeneration in Prg4 mutant mice. This dissertation study of the impact of proteoglycan 4 on the actions of PTH in hematopoiesis, skeletal anabolism, and degenerating joints advances our understanding of the mechanisms mediating PTH biologic actions. Moreover, this body of work further elucidates the role of proteoglycan 4 in physiologic hematopoiesis, skeletogenesis, and joint protection.Ph.D.Oral Health SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/86558/1/novince_1.pd