Aysel A. Fernandes

University of Washington

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David M. Hudson

University of Washington

Audrey McAlinden

Washington University in St. Louis

Russell J. Fernandes

University of Washington

Na Rae Park

Kyungpook National University

Soumya Ravindran

Washington University in St. Louis

Douglas R. Keene

Shriners Hospitals for Children - Portland

Yeon‐Ju Lee

Georgia Institute of Technology

Kyu Sang Joeng

University of Pennsylvania

David T. Corr

Rensselaer Polytechnic Institute

Bon‐Hyeock Koo

University of Pennsylvania

Cooperative Institutions

The University of Texas Southwestern Medical Center

University of Pennsylvania

Organogenesis (United States)

Southwestern Medical Center

California University of Pennsylvania

University of Michigan–Ann Arbor

Creative Commons

Plastic Surgery Hospital

University of Washington

Washington University in St. Louis

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The HIF-1α/PLOD2 axis integrates extracellular matrix organization and cell metabolism leading to aberrant musculoskeletal repair

Bone Research (2024)

Heeseog Kang Amy L. Strong Yuxiao Sun Lei Guo Conan Juan

Abstract While hypoxic signaling has been shown to play a role in many cellular processes, its role in metabolism-linked extracellular matrix (ECM) organization and downstream processes of cell fate after musculoskeletal injury remains to be determined. Heterotopic ossification (HO) is a debilitating condition where abnormal bone formation occurs within extra-skeletal tissues. Hypoxia and hypoxia-inducible factor 1α (HIF-1α) activation have been shown to promote HO. However, the underlying molecular mechanisms by which the HIF-1α pathway in mesenchymal progenitor cells (MPCs) contributes to pathologic bone formation remain to be elucidated. Here, we used a proven mouse injury-induced HO model to investigate the role of HIF-1α on aberrant cell fate. Using single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics analyses of the HO site, we found that collagen ECM organization is the most highly up-regulated biological process in MPCs. Zeugopod mesenchymal cell-specific deletion of Hif1α ( Hoxa11-CreER T2 ; Hif1a fl/fl ) significantly mitigated HO in vivo. ScRNA-seq analysis of these Hoxa11-CreER T2 ; Hif1a fl/fl mice identified the PLOD2/LOX pathway for collagen cross-linking as downstream of the HIF-1α regulation of HO. Importantly, our scRNA-seq data and mechanistic studies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1α deletion. From a translational aspect, a pan-LOX inhibitor significantly decreased HO. A newly screened compound revealed that the inhibition of PLOD2 activity in MPCs significantly decreased osteogenic differentiation and glycolytic metabolism. This suggests that the HIF-1α/PLOD2/LOX axis linked to metabolism regulates HO-forming MPC fate. These results suggest that the HIF-1α/PLOD2/LOX pathway represents a promising strategy to mitigate HO formation.

HIF1A

Hypoxia

Cell fate determination

Hypoxia-Inducible Factors

10.1038/s41413-024-00320-0

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Citations (7)

EVALUATION OF PRODUCTION OF CACTUS PERA (Opuntia Ficus - Indica Mill) IN THE DENSITY PRODUCTION SYSTEM

DOAJ (DOAJ: Directory of Open Access Journals) (2011)

Emmanuel Moreira Pereira Alcides Almeida Ferreira Valdeci Andrade Dantas Luci Cleide Farias Soares Sousa Aysel A. Fernandes

Resumo - O trabalho teve como objetivo na avaliacao da producao da cultura da palma forrageira Opuntia ficus – indica Mill de formade cultivo adensado. A pesquisa foi realizada em situacao de campo, na Escola Agrotecnica do Cajueiro, pertencente ao municipio de Catole do Rocha-PB, Latitude -06° 20' 38'', Longitude 37° 44' 48'‘, com altitude272m.etros, e area de 466,2 km², foi implantado em uma area de 0,5 ha, nos periodos de setembro de 2006 ate agosto de 2007. A producao obtida com a cultura da palma enaltece o plantio adensado, produzindo satisfatoriamente em condicoes de sequeiro. Palavras chaves : sistema adensado, palma forrageira. Worldwide, the cactus pear is used in human food, animal feeding, as a source of energy, in medicine, in the cosmetics industry, in the protection and soil conservation, among other noble uses, such as the manufacture of adhesives, glues, and fibers for handicrafts, paper, dyes, mucilage, antiperspirant and ornamentation. The purpose of the study was to evaluate the production of cactus pear culture Opuntia ficus - indica Mill, the type of crop used was the density. The research was conducted under field conditions in the Agrotechnical School Cajueiro in Catole Rocha-PB, was deployed in an area of 0.5 ha, from September 2006 until August 2007. The production of forage palm in half a hectare in dense system reached 192.5 tons in rainfed system; this result comes from the first cut, and may be influenced by external factors such as cultural adaptation of the region.

Hectare

Mucilage

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Ajuste de equações matemáticas para determinar a área foliar de mudas de Allagopteraarenaria de forma não destrutiva.

S. Dousseau Aysel A. Fernandes L. L. Longue Geralda Pereira Santos R. P. Posse

O objetivo deste estudo foi ajustar equacoes matematicas para estimar de forma nao destrutiva a area foliar de mudas de Allagoptera arenaria a partir das dimensoes lineares do limbo foliar. Para tanto, 205 folhas foram utilizadas sendo obtidas de cada folha as medidas do maior comprimento (C), maior largura (L) e area foliar Observada (AFO). Determinou-se tambem o produto da multiplicacao do comprimento com a largura (CL). Para o ajuste das equacoes, foram utilizadas 175 folhas onde os valores da AFO foram usados como variavel dependente em funcao de C, L, ou CL como variavel independente, sendo ajustados os modelos linear de primeiro grau, quadratico e potencia. Todos os modelos foram validados com base em amostra de 30 folhas separadas para esta finalidade. Assim, a area foliar das mudas de A.arenaria pode ser determinada pela equacao de modelo potencia obtida pelo produto da multiplicacao do comprimento com a largura (CL).

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Characterization of TGFβ1-induced tendon-like structure in the scaffold-free three-dimensional tendon cell culture system

Scientific Reports (2024)

Bon‐Hyeock Koo Yeon‐Ju Lee Na Rae Park Su Chin Heo David M. Hudson

Abstract The biological mechanisms regulating tenocyte differentiation and morphological maturation have not been well-established, partly due to the lack of reliable in vitro systems that produce highly aligned collagenous tissues. In this study, we developed a scaffold-free, three-dimensional (3D) tendon culture system using mouse tendon cells in a differentially adherent growth channel. Transforming Growth Factor-β (TGFβ) signaling is involved in various biological processes in the tendon, regulating tendon cell fate, recruitment and maintenance of tenocytes, and matrix organization. This known function of TGFβ signaling in tendon prompted us to utilize TGFβ1 to induce tendon-like structures in 3D tendon constructs. TGFβ1 treatment promoted a tendon-like structure in the peripheral layer of the constructs characterized by increased thickness with a gradual decrease in cell density and highly aligned collagen matrix. TGFβ1 also enhanced cell proliferation, matrix production, and morphological maturation of cells in the peripheral layer compared to vehicle treatment. TGFβ1 treatment also induced early tenogenic differentiation and resulted in sufficient mechanical integrity, allowing biomechanical testing. The current study suggests that this scaffold-free 3D tendon cell culture system could be an in vitro platform to investigate underlying biological mechanisms that regulate tenogenic cell differentiation and matrix organization.

Matrix (chemical analysis)

10.1038/s41598-024-60221-4

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Citations (2)

Biochemical and Immuno-Histochemical Localization of Type IIA Procollagen in Annulus Fibrosus of Mature Bovine Intervertebral Disc

bioRxiv (Cold Spring Harbor Laboratory) (2021)

Audrey McAlinden David M. Hudson Aysel A. Fernandes Soumya Ravindran Russell J. Fernandes

Abstract For next generation tissue-engineered constructs and regenerative medicine to succeed clinically, the basic biology and extracellular matrix composition of tissues that these repair techniques seek to restore have to be fully determined. Using the latest reagents coupled with tried and tested methodologies, we continue to uncover previously undetected structural proteins in mature intervertebral disc. In this study we show that the “embryonic” type IIA procollagen isoform (containing a cysteine-rich amino propeptide) was biochemically detectable in the annulus fibrosus of both calf and mature steer intervertebral discs, but not in the nucleus pulposus where the type IIB isoform was predominantly localized. Specifically, the triple-helical type IIA procollagen isoform immunolocalized in the outer margins of the inner annulus fibrosus. Triple helical processed type II collagen exclusively localized within the interlamellae regions and with type IIA procollagen in the intra-lamellae regions. Mass spectrometry of the α1 (II) collagen chains from the region where type IIA procollagen localized showed high 3-hydroxylation of Proline-944, a post-translational modification that is correlated with thin collagen fibrils as in the nucleus pulposus. The findings implicate small diameter fibrils of type IIA procollagen in select regions of the annulus fibrosus where it likely contributes to the organization of collagen bundles and structural properties within the type I-type II collagen transition zone.

Procollagen peptidase

Intervertebral Disc

Type I collagen

Type II collagen

Annulus (botany)

Hydroxylation

10.1101/2021.03.26.437279

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Characterization of TGFβ-induced tendon-like structure in scaffold-free three-dimensional tendon cell culture

bioRxiv (Cold Spring Harbor Laboratory) (2022)

Bon‐Hyeock Koo Yeon‐Ju Lee Na Rae Park Su-Jin Heo David M. Hudson

Abstract Tendons transmit mechanical forces between muscle and bone. Their biomechanical function requires high tensile strength provided by highly organized collagen fibers. Tenocytes mainly drive tendon growth via extracellular matrix (ECM) production and organization. The biological mechanisms regulating tenocyte differentiation and morphological maturation have not been well-established, partly due to the lack of reliable in vitro systems that produce highly aligned collagenous tissues. In this study, we developed a scaffold-free, three-dimensional (3D) tendon culture system using mouse tendon cells and a differentially adherent growth channel. TGFβ treatment promoted tendon-like structure in the peripheral layer of the constructs with decreased cell density, decreased cell proliferation, increased thickness, and more elongated cells within highly aligned extracellular matrix. The constructs were used to understand the function of TGFβ signaling in tenogenic differentiation, collagen fibrillogenesis, and biomechanical properties. This scaffold-free 3D constructs system can serve as a reliable in vitro system to study underlying biological mechanisms that regulate cellular and matrix maturation in tendon development and growth.

Fibrillogenesis

Matrix (chemical analysis)

10.1101/2022.06.08.495368

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Biochemical and immuno-histochemical localization of type IIA procollagen in annulus fibrosus of mature bovine intervertebral disc

Matrix Biology Plus (2021)

Audrey McAlinden David M. Hudson Aysel A. Fernandes Soumya Ravindran Russell J. Fernandes

For next generation tissue-engineered constructs and regenerative medicine to succeed clinically, the basic biology and extracellular matrix composition of tissues that these repair techniques seek to restore have to be fully determined. Using the latest reagents coupled with tried and tested methodologies, we continue to uncover previously undetected structural proteins in mature intervertebral disc. In this study we show that the "embryonic" type IIA procollagen isoform (containing a cysteine-rich amino propeptide) was biochemically detectable in the annulus fibrosus of both calf and mature steer caudal intervertebral discs, but not in the nucleus pulposus where the type IIB isoform was predominantly localized. Specifically, the triple-helical type IIA procollagen isoform immunolocalized in the outer margins of the inner annulus fibrosus. Triple helical processed type II collagen exclusively localized within the inter-lamellae regions and with type IIA procollagen in the intra-lamellae regions. Mass spectrometry of the α1(II) collagen chains from the region where type IIA procollagen localized showed high 3-hydroxylation of Proline-944, a post-translational modification that is correlated with thin collagen fibrils as in the nucleus pulposus. The findings implicate small diameter fibrils of type IIA procollagen in select regions of the annulus fibrosus where it likely contributes to the organization of collagen bundles and structural properties within the type I-type II collagen transition zone.

Procollagen peptidase

Type II collagen

Intervertebral Disc

Type I collagen

Annulus (botany)

Hydroxylation

10.1016/j.mbplus.2021.100077

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Citations (2)

É VIÁVEL O USO DOS SEDIMENTOS DA BARRAGEM DO AÇUDE DO IFMA - CAMPUS CODÓ COMO SUBSTRATO NA PRODUÇÃO DE PIMENTA?

BRUNNA KAETELY WALERIA DA SILVA ARAUJO Victorio Alessandro de Leão Loeschke Moraes Izadora Portela de Sousa Fernandes Gisela Santos Aysel A. Fernandes

10.31692/2526-7701.ixcointerpdvagro.0202

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