Jonathan W Lowery

• PhD
• Professor (Associate) at Marian University - Indiana

Context Sarcopenia is a disease characterized by low muscle mass and function that places individuals at greater risk of disability, loss of independence, and death. Current therapies include addressing underlying performance issues, resistance training, and/or nutritional strategies. However, these approaches have significant limitations, and chro...

Achieving bone union remains a significant clinical dilemma. The use of osteoinductive agents, specifically bone morphogenetic proteins (BMPs), has gained wide attention. However, multiple side effects, including increased incidence of cancer, have renewed interest in investigating alternatives that provide safer, yet effective bone regeneration. H...

Bone mass is determined by the relative balance of action between osteoblasts, which deposit bone matrix, and osteoclasts, which resorb bone matrix. Imbalance in these actions leads to conditions of high or low bone mass. Osteoporosis, i.e., low bone mass, is a common medical condition that places individuals at elevated risk of fracture and greate...

The role of parathyroid hormone (PTH)-related protein (PTHrP) in breast cancer remains controversial, with reports of PTHrP inhibiting or promoting primary tumor growth in preclinical studies. Here, we provide insight into these conflicting findings by assessing the role of specific biological domains of PTHrP in tumor progression through stable ex...

Low back pain (LBP) is a common musculoskeletal complaint that can impede physical function and mobility. Current management often involves pain medication, but there is a need for non-pharmacological and non-invasive interventions. Soft tissue manipulation (STM), such as massage, has been shown to be effective in human subjects, but the molecular...

Low back pain (LBP) is a common musculoskeletal complaint that can impede physical function and mobility. Current management often involves pain medication, but there is a need for non-pharmacological and non-invasive interventions. Soft tissue manipulation (STM) such as massage has been shown to be effective in human subjects, but the molecular me...

Global loss of the neuropeptide Neuromedin-U (NMU) is associated with increased bone formation and high bone mass in male and female mice by twelve weeks of age, suggesting that NMU suppresses osteoblast differentiation and/or activity in vivo. NMU is highly expressed in numerous anatomical locations including the skeleton and the hypothalamus. Thi...

Involvement in research is regarded as a high-impact educational practice, which, for medical professionals, is associated with sharpened critical thinking and life-long learning skills, greater appreciation for evidence-based medicine, and better clinical competence scores. However, there are limited data regarding the research experience and/or i...

Context It is important for colleges of osteopathic medicine (COMs) to provide opportunities for osteopathic medical students (OMSs) to conduct research under the guidance of professional researchers. However, COMs historically lag behind allopathic medical schools in research offerings for medical students. The literature would benefit from a syno...

This mini-review summarizes the available information regarding the impact of caloric restriction (CR) and/or intermittent fasting (IF) on bone health. CR and IF are dietary interventions used in rehabilitative healthcare for augmenting weight loss and also proposed for recovery of conditions such as stroke and heart failure. CR restricts the total...

A significant amount of attention has been brought to the endocrine-like function of skeletal muscle on various tissues, particularly with bone. Several lines of investigation indicate that the physiology of both bone and muscle systems may be regulated by a given stimulus, such as exercise, aging, and inactivity. Moreover, emerging evidence indica...

Neuromedin-U (NMU) is an evolutionarily conserved peptide that regulates varying physiologic effects including blood pressure, stress and allergic responses, metabolic and feeding behavior, pain perception, and neuroendocrine functions. Recently, several lines of investigation implicate NMU in regulating bone remodeling. For instance, global loss o...

Individuals with osteoporosis, i.e., low bone mass, are at enhanced risk for fracture, disability, and death. Hospitalizations for osteoporotic fractures exceed those for heart attack, stroke, and breast cancer. Osteoporosis rates are predicted to increase due to an aging global population yet there are limited pharmacological treatment options for...

The authors present a stereotypical case presentation of X-linked hypophosphatemia (XLH) and provide a review of the pathophysiology and related pharmacology of this condition, primarily focusing on the FDA-approved medication burosumab. XLH is a renal phosphate wasting disorder caused by loss of function mutations in the PHEX gene (phosphate-regul...

The authors present a stereotypical case presentation of x-linked hypophosphatemia (XLH) and provide a review of the pathophysiology and related pharmacology of this condition, primarily focusing on the FDA-approved medication burosumab. XLH is a renal phosphate wasting disorder caused by loss of function mutations in the PHEX gene (phosphate-regul...

Objective: Soft tissue manual therapies are commonly utilized by osteopathic physicians, chiropractors, physical therapists and massage therapists. These techniques are predicated on subjecting tissues to biophysical mechanical stimulation but the cellular and molecular mechanism(s) mediating these effects are poorly understood. Previous studies e...

Context: There are limited data regarding the experiences of and attitudes toward research participation among osteopathic medical students despite rapidly increasing enrollment and expansion of the number of osteopathic medical schools. Objective: To assess first-year osteopathic medical students' experience with research, their interest in it,...

Osteoporosis is a disease of low bone mass that places individuals at enhanced risk for fracture, disability, and death. Osteoporosis rates are expected to rise significantly in the coming decades yet there are limited pharmacological treatment options, particularly for long-term management of this chronic condition. The drug development pipeline i...

Objective Soft tissue manual therapies such as massage and myofascial release are commonly utilized by osteopathic physicians, chiropractors, physical therapists and massage therapists. These techniques are predicated on subjecting tissues to biophysical mechanical stimulation but the cellular and molecular mechanism(s) mediating these effects are...

Objective Soft tissue manual therapies are commonly utilized by osteopathic physicians, chiropractors, physical therapists and massage therapists. These techniques are predicated on subjecting tissues to biophysical mechanical stimulation but the cellular and molecular mechanism(s) mediating these effects are poorly understood. A series of previous...

Objective Soft tissue manual therapies are commonly utilized by osteopathic physicians, chiropractors, physical therapists and massage therapists. These techniques are predicated on subjecting tissues to biophysical mechanical stimulation but the cellular and molecular mechanism(s) mediating these effects are poorly understood. Previous studies est...

Objective: The bone morphogenetic protein (BMP) signaling pathway comprises the largest subdivision of the transforming growth factor (TGFβ) superfamily. BMP signaling plays essential roles in both embryonic development and postnatal tissue homeostasis. Dysregulated BMP signaling underlies human pathologies ranging from pulmonary arterial hyperten...

Osteoporosis, a disease of low bone mass, places individuals at enhanced risk for fracture, disability, and death. In the USA, hospitalizations for osteoporotic fractures exceed those for heart attack, stroke, and breast cancer and, by 2025, the number of fractures due to osteoporosis is expected to rise to nearly three million in the USA alone. Ph...

Bone morphogenetic proteins (BMPs) constitute the largest subdivision of the transforming growth factor-β family of ligands. BMPs exhibit widespread utility and pleiotropic, context-dependent effects, and the strength and duration of BMP pathway signaling is tightly regulated at numerous levels via mechanisms operating both inside and outside the c...

It is estimated that more than 500,000 bone grafting surgeries occur annually in the US to repair or replace defects. Significant progress has been made in this field in recent years, thus making it opportune to survey the technologies currently available and highlight promising future strategies. Here, we offer a timely summarization of the field...

The taste receptor type 1 (TAS1R) family of heterotrimeric G protein-coupled receptors participates in monitoring energy and nutrient status. TAS1R member 3 (TAS1R3) is a bi-functional protein that recognizes amino acids such as L-glycine and L-glutamate or sweet molecules such as sucrose and fructose when dimerized with TAS1R member 1 (TAS1R1) or...

Satellite cells are skeletal muscle stem cells that provide myonuclei for postnatal muscle growth, maintenance, and repair/regeneration in adults. Normally, satellite cells are mitotically quiescent, but they are activated in response to muscle injury, in which case they proliferate extensively and exhibit upregulated expression of the transcriptio...

Bone morphogenetic proteins (BMPs) constitute the largest subdivision of the transforming growth factor (TGF)-β family of ligands and exert most of their effects through the canonical effectors Smad1, 5, and 8. Appropriate regulation of BMP signaling is critical for the development and homeostasis of numerous human organ systems. Aberrations in BMP...

The special sense of taste guides and guards food intake and is essential for body maintenance. Salty and sour tastes are sensed via ion channels or gated ion channels while G protein-coupled receptors (GPCRs) of the taste receptor type 1 (T1R) family sense sweet and umami tastes and GPCRs of the taste receptor type 2 (T2R) family sense bitter tast...

The transforming growth factor β (TGF-β) superfamily is a large group of signaling molecules that participate in embryogenesis, organogenesis, and tissue homeostasis. These molecules are present in all animal genomes. Dysfunction in the regulation or activity of this superfamily's components underlies numerous human diseases and developmental defec...

Bone morphogenetic proteins (BMPs) constitute the largest subdivision of the TGF- β family of ligands and are unequivocally involved in regulating stem cell behavior. Appropriate regulation of canonical BMP signaling is critical for the development and homeostasis of numerous human organ systems, as aberrations in the BMP pathway or its regulation...

Osteoblasts and bone marrow adipocytes originate from bone marrow mesenchymal stem cells (BMMSCs) and there appears to be a reciprocal relationship between adipogenesis and osteoblastogenesis. Alterations in the balance between adipogenesis and osteoblastogenesis in BMMSCs wherein adipogenesis is increased relative to osteoblastogenesis are associa...

Specific reports of BMP pathway modulation and related applications are provided in the supplemental material. Specific applications highlighted are meant to be representative rather than exhaustive of the field and no endorsement by the authors of any particular application should be inferred.

T1R3 is a T1R class of G protein-coupled receptors, composing subunit of the umami taste receptor when complexed with T1R1. T1R3 was originally discovered in gustatory tissue but is now known to be expressed in a wide variety of tissues and cell types such the intestine, pancreatic β-cells, skeletal muscle, and heart. In addition to taste recogniti...

Background Bone morphogenetic proteins (BMPs) induce ectopic bone formation in vivo and osteoblast differentiation of various cells in vitro. Therefore, BMPs are thought to be useful in bone regeneration medicine and for treating bone-related diseases. However, clinical application of BMPs is not widespread. Highlight BMP signal transduction and B...

Imbalances in the ratio of bone morphogenetic protein (BMP) versus activin and TGFb signaling are increasingly associated with human diseases yet the mechanisms mediating this relationship remain unclear. The type 2 receptors ACVR2A and ACVR2B bind BMPs and activins but the type 2 receptor BMPR2 only binds BMPs, suggesting that type 2 receptor util...

Imbalances in the ratio of BMP versus Activin/TGFβ signaling are increasingly associated with human diseases yet the mechanisms mediating this relationship remain unclear. The type 2 receptors ACVR2A/B bind BMPs and Activins but the type 2 receptor BMPR2 only binds BMPs, suggesting that type 2 receptor utilization might play a role in mediating the...

Supplementary Table S1 Outline of hBMPR2 expression plasmids utilized and their construction

Supplementary Figure S1 Conservation of N-linked glycosylation sites in BMPR2 orthologs. Alignment comparison of BMPR2 orthologs. All available amino acid sequences of full-length BMPR2 were obtained from the GenBank database and aligned using MUSCLE [54] in MEGA5 [55]

The bone morphogenetic protein (BMP) signaling pathway is essential for normal development and tissue homeostasis. BMP signal transduction occurs when ligands interact with a complex of type 1 and type 2 receptors to activate downstream transcription factors. It is well established that a single BMP receptor may bind multiple BMP ligands with varyi...

More than 200 heterozygous mutations in the type 2 BMP receptor gene, BMPR2, have been identified in patients with Heritable Pulmonary Arterial Hypertension (HPAH). More severe clinical outcomes occur in patients with BMPR2 mutations by-passing nonsense-mediated mRNA decay (NMD negative mutations). These comprise 40% of HPAH mutations and are predi...

The Bone Morphogenetic Protein (BMP) pathway is an ancient, multi‐member signaling cascade whose basic components are found in all animals. One member, BMP3, which is found only in deuterostomes, serves a unique role as an antagonist to both the canonical BMP and Activin pathways. However, the mechanisms and cis‐regulatory regions controlling BMP3...

Objective: Bone morphogenetic proteins (BMPs) are a family of secreted signaling molecules that regulate a wide variety of physiological processes, including bone formation and endothelial function. A previous investigation examining the role of BMPs using transgenic mouse models to simulate hypoxic pulmonary hypertension demonstrated that Bmp2 a...

The Bone Morphogenetic Protein (BMP) pathway is a multi-member signaling cascade whose basic components are found in all animals. One member, BMP3, which arose more recently in evolution and is found only in deuterostomes, serves a unique role as an antagonist to both the canonical BMP and Activin pathways. However, the mechanisms that control BMP3...

Determination and individual nucleotide conservation of the minimal Bmp3 upstream ECR (minECR) present in all RefSeq mammals. BLASTN (Version 2.2.26+) was used to align the M. musculus: H. sapiens CoreECR sequence to all sixteen available eutherian mammal RefSeq genomes in order to identify the Bmp3 upstream ECR shared with M. musculus. Each full-l...

Primers used for firefly luciferase reporter plasmid construction. (XLSX)

Nucleotide alignments of the Bmp3 5 kb upstream regions between M. musculus and other mammals. (XLS)

Conservation analysis of the Bmp3 upstream Evolutionary Conserved Region (ECR) in RefSeq animal genomes. (XLS)

Conservation analysis of the minimal Bmp3 upstream Evolutionary Conserved Region (minECR) in all available animal genomes. (XLS)

Bmp3 expression analysis. RT-PCR for Bmp3 in HEK293T cells (A), UMR-106 cells (B), primary mouse calvarial osteoblasts(cOBs, C), and C2C12 cells 9D) compared to Hprt housekeeping control. Newborn mouse hind limb cDNA was used as a positive control in all experiments (only shown in A). Intervening lanes from a single gel removed in A (indicated by w...

Transcription factor binding sites upstream of M. musculus Bmp3. (XLSX)

Transcription factor binding sites conserved between M. musculus and H. sapiens in the region upstream of Bmp3. (XLS)

Transcription factor binding sites in the consensus minimal Bmp3 upstream ECR and conservation in Rodents/Primates. (XLSX)

Genetic studies in mice demonstrate that the bone morphogenetic protein (Bmp) signaling pathway plays critical roles in regulating embryonic vascular development. Many of the pathways regulating vascular development are reactivated in the adult following injury, suggesting that defective Bmp signaling could also play a role in vascular diseases. De...

Genetic studies in mice demonstrate that the bone morphogenetic protein (Bmp) signaling pathway plays critical roles in regulating embryonic vascular development. Many of the pathways regulating vascular development are reactivated in the adult following injury, suggesting that defective Bmp signaling could also play a role in vascular diseases. De...

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disease in which bone is formed in soft tissues through heterotopic ossification (HO). HO is often a problem for patients who have received a traumatic insult, either to musculoskeletal tissues (traumatic HO) or to the skin or spinal cord (neurologic HO). Although trauma-induc...

Enhancing bone morphogenetic protein (BMP) signaling increases bone formation in a variety of settings that target bone repair. However, the role of BMP in the maintenance of adult bone mass is not well understood. Targeted disruption of BMP3 in mice results in increased trabecular bone formation, whereas transgenic overexpression of BMP3 in skelet...

Initiation of BMP signaling is dependent upon activation of Type I BMP receptor by constitutively active Type II BMP receptor. Three Type II BMP receptors have been identified; Acvr2a and Acvr2b serve as receptors for BMPs and for activin-like ligands whereas BMPR-II functions only as a BMP receptor. As BMP signaling is required for endochondral os...

While new roles for the adult skeleton as an endocrine organ continue to emerge, our understanding of how bone homeostasis is maintained is also changing. Here we focus on BMP2, a molecule identified by its ability to induce bone formation at extraskeletal sites. We detail specific roles for BMP2 in the adult skeleton, where it acts to regulate the...

Bone morphogenetic protein (BMP) signaling has been linked to the development of pulmonary hypertension (PH). Inhibitors of differentiation (ID) proteins (ID1-4) are a family of basic helix-loop-helix transcription factors that are downstream targets of the BMP signaling pathway, but the role that ID proteins play in the development of PH is unknow...

Genetic and functional studies indicate that common components of the bone morphogenetic protein (BMP) signaling pathway play critical roles in regulating vascular development in the embryo and in promoting vascular homeostasis and disease in the adult. However, discrepancies between in vitro and in vivo findings and distinct functional properties...

Aberrations in BMP signaling have been implicated in the etiology of Pulmonary Arterial Hypertension. However, the specific role of BMP signaling in the normal pulmonary vasculature is not known. Here, we evaluate the necessity of the downstream BMP target Id1 in the vascular remodeling of murine hypoxic pulmonary hypertension (PH). Id1, which is s...

Patients with Familial Pulmonary Hypertension have mutations in the BMP receptor, BMPR2, but it is unknown how these mutations cause disease. These observations also raise questions as to the role of BMPR2 signaling in other forms of pulmonary hypertension (PH). To address this, we evaluated the regulation and function of Bmpr2 ligands in a mouse m...

The bone morphogenetic protein (BMP) type 2 receptor ligand, Bmp2, is upregulated in the peripheral pulmonary vasculature during hypoxia-induced pulmonary hypertension (PH). This contrasts with the expression of Bmp4, which is expressed in respiratory epithelia throughout the lung. Unlike heterozygous null Bmp4 mice (Bmp4(LacZ/+)), which are protec...

Patients with familial pulmonary arterial hypertension inherit heterozygous mutations of the type 2 bone morphogenetic protein (BMP) receptor BMPR2. To explore the cellular mechanisms of this disease, we evaluated the pulmonary vascular responses to chronic hypoxia in mice carrying heterozygous hypomorphic Bmpr2 mutations (Bmpr2 delta Ex2/+). These...