About

Dr. Vicki Rosen is a professor and chair of the Department of Developmental Biology at Harvard School of Dental Medicine (HSDM), where she has served since 2001. She was named the first incumbent of the Doctors Samuel and Ida Gelfand Professorship in October 2024, an endowed position recognizing scholars in emerging areas of scientific inquiry. Rosen is renowned for her pioneering research in bone biology, particularly her work on bone morphogenetic proteins (BMPs) and their roles in the development, maintenance, and repair of musculoskeletal tissues. Before joining HSDM, she was part of the research team at Genetics Institute that identified the BMP genes in 1988. As a respected scientist, educator, and academic leader, she was the first female full professor at HSDM and has served as interim dean, leading the School through the early months of the COVID-19 pandemic. In addition to her research, Rosen is deeply committed to mentoring students and postdoctoral fellows across multiple disciplines, including DMD, MD, and PhD programs, and is a principal faculty member of the Harvard Stem Cell Institute.

Research topics

• Biology
• Anatomy
• Computer Science
• Artificial Intelligence
• Cell biology
• Medicine
• Pathology
• Cancer research
• Internal medicine

Selected publications

• Paracrine Action of Bone Morphogenetic Protein 3 in Pulmonary Arterial Hypertension

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-18 · 1 citations

  preprintOpen access

  ABSTRACT Background Despite recent advancements in the management of pulmonary arterial hypertension (PAH), the disease remains devastating, with limited survival. Although the Bone Morphogenetic Protein (BMP) signaling pathway is known to play an important role in PAH, our current understanding of this pathway remains limited. Methods We assessed BMP3 levels in the lungs of mice, rats, and pigs with pulmonary hypertension, and in pulmonary vascular cells from human patients with PAH. We performed in vitro studies on human pulmonary artery smooth muscle cells (hPASMCs) and human pulmonary artery endothelial cells (hPAECs) derived from healthy donors and from patients with PAH. We generated mice with global or SMC-specific deletion of BMP3. Recombinant BMP3 protein and adeno-associated viruses (AAV) were used to overexpress BMP3 in two different models of PAH in rodents. Magnetic resonance imaging, cardiac hemodynamics, morphometric, and histological measurements were performed to evaluate the effects of BMP3 on cardiac function and pulmonary vascular remodeling. Results BMP3 is predominantly expressed in PASMCs and is downregulated in PAH. In vitro, conditioned medium from siRNA-BMP3-transfected hPASMCs increased hPAECs migration and proliferation, while PASMC-derived BMP3 inhibited PAH-diseased PAEC dysfunction. In both global and SMC-specific BMP3-deficient mice, exposure to a model of PAH exacerbated cardiac and pulmonary vascular remodeling in middle-aged mice. An intraperitoneally injected recombinant BMP3 prevented and reversed PAH in mice. A lung-targeted overexpression of BMP3, via AAV1-BMP3, reversed pulmonary vascular remodeling and inhibited cardiac dysfunction in mice and rats. Mechanistically, BMP3 activated the BMP/Smad1,5,8 pathway, inhibited the TGF-β/Smad2,3 pathway, and decreased the expression of cell cycle genes in hPAECs and in the lungs of BMP3-treated animals with PAH. Conclusions Our findings provide evidence that BMP3 overexpression attenuates pulmonary vascular remodeling and inhibits cardiac dysfunction by restoring the balance between the TGF-β and BMP pathways through a cell-cell communication mechanism, offering a novel therapeutic pathway for PAH. Clinical Perspective What is New? BMP3 is downregulated in the lungs of mice, rats, and pigs with pulmonary hypertension and in pulmonary artery smooth muscle cells of patients with PAH. BMP3 acts as a paracrine factor between pulmonary vascular cells. Overexpression of BMP3 decreases pulmonary vascular remodeling and reverses cardiac dysfunction in PAH-diseased rodents. BMP3 acts by restoring the balance between the TGF-β/Smad2,3 pathway and the BMP/Smad1,5,8 pathway What Are the Clinical Implications? BMP3 represents a promising disease-modifying agent with potential for clinical translation in the treatment of PAH. Overexpressing BMP3 with Adeno-Associated Viruses has therapeutic potential to treat PAH.

  PublisherDOI

• Adipocyte cell therapy targeting BMP signaling alleviates fibroadipose tissue deposition in secondary lymphedema

  Molecular Therapy · 2025-09-23

  articleOpen access
  PublisherOA PDFDOI

• Abstract 4368485: BMP3 Overexpression Attenuates Pulmonary Arterial Hypertension

  Circulation · 2025-11-03

  article

  Backgound: Pulmonary arterial hypertension (PAH), a rare and progressive subtype of pulmonary hypertension (PH), leads to right heart failure and, ultimately, death. PH is defined by a mean pulmonary arterial pressure greater than 20 mmHg at rest, assessed via right heart catheterization. Methods: We investigated BMP3 expression in lung tissues from multiple animal models of PAH (mice, rats, pigs) and in pulmonary vascular cells from PAH patients. Functional studies were conducted using hPASMCs and hPAECs from healthy individuals and PAH patients. BMP3 loss- and gain-of-function models were generated via genetic deletion and BMP3 overexpression (recombinant protein and AAV1-mediated gene transfer). Phenotypic effects were assessed using hemodynamics, MRI, and histological analyses. Results: BMP3 was primarily expressed in PASMCs and found to be downregulated in PAH. Loss of BMP3 in PASMC enhanced the proliferation and migration of hPAEC, whereas BMP3 overexpression in PASMC restored endothelial function. Both global and SMC-specific BMP3 knockout mice exhibited worsened pulmonary vascular remodeling and right ventricular dysfunction in response to PAH stimuli. Therapeutically, systemic BMP3 administration and lung-specific AAV1-BMP3 delivery inhibited PAH. Mechanistically, BMP3 activated the protective BMP/Smad1/5/8 signaling pathway while suppressing the pro-fibrotic TGF-β/Smad2/3 pathway. Conclusion: BMP3 is a critical modulator of pulmonary vascular and cardiac remodeling in PAH. Restoration of BMP3 signaling offers a promising therapeutic avenue by rebalancing BMP and TGF-β pathways through paracrine cell-cell interactions.

  PublisherDOI

• CXXC Finger Protein 1 drives BMP signaling and progenitor cell differentiation during limb development

  Developmental Biology · 2025-09-05

  articleOpen access
  PublisherOA PDFDOI

• Complex Regulatory Interactions at <scp> <i>GDF5</i> </scp> Shape Joint Morphology and Osteoarthritis Disease Risk

  Arthritis & Rheumatology · 2025-05-13 · 8 citations

  articleOpen access

  OBJECTIVE: The objective of this study was to reveal causal-level osteoarthritis (OA) disease biology by targeting regulatory interactions at GDF5. METHODS: By investigating different GDF5 regulatory regions (R2, R3-R5, R7-R9, R18-R20, GROW1), we explored their functional impacts on gene expression and joint morphology in vivo and in vitro. We additionally modeled OA variants in said enhancers in in vitro and in vivo mouse models for expression and disease effects. RESULTS: For all regulatory regions, we found evidence of activation and repression between or within said regions that impacted patterns of joint-specific expression. Examples are as follows: (1) the R4 enhancer, although considered to be activating, has dual roles repressing expression in adjacent tissues and sites, and (2) growth plate-specific expression patterns by the GROW1 regulatory region are confined by adjacent sequences to restrict its expression to the perichondrium. We next targeted different regions and variants in vivo. Testing the R2de region resulted in ~40% reduction in Gdf5 expression and joint morphology changes but no increase in OA risk; likewise, modeling the most cited OA risk variant (rs143384) in mice had no impact on expression, joint morphology, or disease. However, we identified epistatic interactions between this rs143384 risk variant and downstream disease risk variants lying within regulatory regions subject to repression, which compound to impact expression. CONCLUSION: These findings, at the best studied OA locus to date, serve as lessons on the nature of how gene regulatory interactions and local epistasis work in the etiology of OA disease risk, and that assessment of individual variants of high genome-wide association study significance need not alone be considered causal.

  PublisherOA PDFDOI

• Acute regulation of murine adipose tissue lipolysis and insulin resistance by the TGFβ superfamily protein GDF3

  Nature Communications · 2025-05-13 · 3 citations

  articleOpen access

  TGFβ superfamily proteins can affect cellular differentiation, thermogenesis, and fibrosis in mammalian adipose tissue. Here we describe a role for Growth Differentiation Factor 3 (GDF3) on mature adipocyte biology. We find inducible GDF3 loss of function in obese adult mice leads to reduced lipolysis, improved glucose tolerance, and reduced glycemic variability. The effects on lipolysis are driven by lower levels of β3-adrenergic receptor, decreased cAMP and PKA signaling. GDF3 is an ALK5, ALK7, ACVR2A and ACVR2B agonist and also a BMPR2 antagonist. Unlike ALK7 or activin E knockouts, acute GDF3 loss of function does not affect body weight or energy balance but significantly improves metabolic health. These results suggest that blocking GDF3 can improve metabolic health independent of body weight and food intake, an intriguing new model for developing anti-diabetic therapies. Together these results provide much-needed clarity to both the molecular pathways involved in GDF3 signaling and its physiological effects.

  PublisherOA PDFDOI

• Effects of dexamethasone and IGF-1 on post-traumatic osteoarthritis-like catabolic changes in a human cartilage-bone-synovium microphysiological system in space and ground control tissues on earth

  Frontiers in Space Technologies · 2024-03-14 · 3 citations

  articleOpen access

  Post-traumatic Osteoarthritis (PTOA) results from traumatic joint injuries (such as an ACL rupture). Mechanical impact and an immediate synovial inflammatory response can result in joint tissue degradation and longer-term progression to PTOA. Astronauts are susceptible to increased exercise-related joint injuries leading to altered musculoskeletal physiology, further escalated due to microgravity and increased exposure to ionizing radiation. We applied a human Cartilage-Bone-Synovium (CBS) coculture model to test the potential of low-dose dexamethasone (Dex) and IGF-1 in ameliorating PTOA-like degeneration on Earth and the International Space Station-National Laboratory (ISS-NL, ISS for short). CBS cocultures were established using osteochondral plugs (CB) subjected to compressive impact injury (INJ) followed by coculture with synovium (S) explants. Study groups consisted of control (CB); disease [CBS + INJ]; treatment [CBS + INJ + Dex + IGF-1]; and drug-safety [CB + Dex + IGF-1]. Outcome measures included cell viability, altered matrix glycosaminoglycans (GAG) and collagens, multiplex-ELISA quantification of released cytokines, histopathology, and metabolomic and proteomic analyses of spent media. A 21-day study on ISS-NL explored PTOA-like pathogenesis and treatment in microgravity. Tissue cards for study groups were cultured in custom-built culture chambers within multi-use variable-g platforms (MVPs). A marked upregulation in the release of inflammatory cytokines and tissue-GAG loss was observed in CBS + INJ groups in space and ground controls utilizing tissues from the same donors, similar to that reported in a previous multi-donor study on Earth; these changes were partly ameliorated by Dex + IGF-1, but with donor variability. Metabolomic and proteomic analyses revealed an array of distinct differences between metabolites/proteins released to the medium in Space versus on Earth.

  PublisherOA PDFDOI

• The role of GDF5 in regulating enthesopathy development in the <i>Hyp</i> mouse model of XLH

  Journal of Bone and Mineral Research · 2024-06-05 · 1 citations

  articleOpen access

  X-linked hypophosphatemia (XLH) is caused by mutations in PHEX, leading to rickets and osteomalacia. Adults affected with XLH develop a mineralization of the bone-tendon attachment site (enthesis), called enthesopathy, which causes significant pain and impaired movement. Entheses in mice with XLH (Hyp) have enhanced bone morphogenetic protein (BMP) and Indian hedgehog (IHH) signaling. Treatment of Hyp mice with the BMP signaling blocker palovarotene attenuated BMP/IHH signaling in Hyp entheses, thus indicating that BMP signaling plays a pathogenic role in enthesopathy development and that IHH signaling is activated by BMP signaling in entheses. It was previously shown that mRNA expression of growth/differentiation factor 5 (Gdf5) is enhanced in Hyp entheses at P14. Thus, to determine a role for GDF5 in enthesopathy development, Gdf5 was deleted globally in Hyp mice and conditionally in Scx + cells of Hyp mice. In both murine models, BMP/IHH signaling was similarly decreased in Hyp entheses, leading to decreased enthesopathy. BMP/IHH signaling remained unaffected in WT entheses with decreased Gdf5 expression. Moreover, deletion of Gdf5 in Hyp entheses starting at P30, after enthesopathy has developed, partially reversed enthesopathy. Taken together, these results demonstrate that while GDF5 is not essential for modulating BMP/IHH signaling in WT entheses, inappropriate GDF5 activity in Scx + cells contributes to XLH enthesopathy development. As such, inhibition of GDF5 signaling may be beneficial for the treatment of XLH enthesopathy.

  PublisherOA PDFDOI

• 04. Development Of A Bone Marrow-resident Cell Therapy For Tissue Repair During Genetic Heterotopic Ossification

  Plastic & Reconstructive Surgery Global Open · 2024-04-01

  articleOpen access

  Purpose: Fibrodysplasia Ossificans Progressiva (FOP) is a rare genetic disorder characterized by a R206H mutation in the ACVR1 receptor which causes progressive heterotopic ossification (HO) where muscle, tendons, and ligaments are slowly replaced by bones causing loss of mobility, difficulty in speaking, eating, and breathing. We study whether isogenic bone marrow cells from donor FOP mice can be transplanted into recipient FOP mice and whether the transplanted cells traffic to the site of FOP during inflammation. Furthermore, we also examine the changes in differentiation pathway of hematopoietic stem cells (HSCs) in response to BMP and Activin A. We explore the potential of isolating and modifying FOP patient bone marrow cells to produce anti-Activin A protein in response to Activin A and transplant them back for autonomous delivery of anti-Activin-A peptide to the sites of FOP. Methods: 2 donor UBC-Cre(+)/R206H(+)/tdTomato(+) FOP mice (1 male, 1 female) and 3 recipient UBC-Cre(+)/R206H(+)/tdTomato(-) FOP mice (2 male, 1 female) underwent 4 days of tamoxifen injection (100ul of 20mg/ml solution) to express the ACVR1[R206H] mutation. Bone marrow cells were extracted from donor mice and transplanted into recipient mice following 4 days of Busulfan reconditioning (10mg/kg) via i.p. injection for bone marrow ablation. Cardiotoxin was injected three weeks post busulfan treatment to induced FOP in recipients. Animals were euthanized after 3 weeks and hindlimbs were harvested, sectioned, and imaged using confocal microscopy. Tissue sections were stained with anti-CD45 and anti-PDGFRa antibodies to identify the identity of trafficked cells. HSCs were isolated from WT mice and grown in presence of 25ng/ml BMP-2, BMP-4, Activin A, or untreated control for five days. Cells were stained with anti CD11, TER11, CD45R, Ly-6G, and CD3 HSC lineage-specific markers and analyzed using flow cytometry. Results: Images from hindlimb sections showed fluorescent cells from donor trafficking to the site of FOP. The trafficked cells were positive for CD45, an HSC lineage marker, but not positive for PDGFRa, a mesenchymal stem cell lineage marker. Flow cytometric analysis revealed that treatment of HSCs with Activin A, BMP-2, or BMP-4 does not change its differentiation pattern. Population of HSC lineage marker positive and negative cells remained the same with or without the treatment. Conclusion: The presence of fluorescent CD45 positive cells at the site of FOP reveals that the donor cells trafficked to the site of injury. bone marrow-resident cell therapy may be able to traffic to sites at risk for ectopic bone formation and assist with tissue repair.

  PublisherDOI

• 6443 The Role of GDF5 in Regulating Enthesopathy Development in the Hyp mouse Model of XLH

  Journal of the Endocrine Society · 2024-10-01 · 1 citations

  articleOpen access

  Abstract Disclosure: A. Hughes: None. M. Sorsby: None. S. Almardini: None. S. Venkat: None. A. Alayyat: None. M. Rahman: None. J. Baker: None. R. Rana: None. V. Rosen: None. E.S. Liu: Advisory Board Member; Self; Ascendis Pharma. Other; Self; Inozyme - DSMB. X-linked hypophosphatemia (XLH) is characterized by high serum FGF23 levels, impaired production of 1,25 dihydroxyvitamin D, and hypophosphatemia. Up to 60% of adults with XLH develop enthesopathy, which is a mineralization of the bone-tendon attachment site, that causes significant pain and impaired mobility. We previously showed that entheses from mice with XLH (Hyp) have an expansion of hypertrophic appearing enthesopathy cells (HECs) that stain positive for cartilage proteoglycans (Safranin O) and alkaline phosphatase activity (ALP+). The HECs have enhanced bone morphogenetic protein (BMP) and Indian hedgehog (IHH) signaling, implicating these pathways which regulate chondrogenesis in XLH enthesopathy development. Therefore, Hyp mice were treated daily with palovarotene, a retinoid acid gamma receptor agonist that blocks BMP signaling, from postnatal day (P) 7 (prior to enthesopathy development) to P30. Treated Hyp entheses normalized BMP/IHH signaling, indicating that BMP signaling plays a pathogenic role in XLH enthesopathy development and that IHH signaling is activated by BMP signaling in entheses.We previously showed that mRNA expression of BMP/GDF factor Gdf5 is increased in Hyp entheses P14. In the current studies, we performed RNAscope on WT and Hyp entheses, demonstrating that Gdf5 expression is similarly robust in embryonic entheses but decreases dramatically postnatally by P14. While Gdf5 expression is similar between WT and Hyp entheses e16.5 and P2, it is enhanced in P14 Hyp entheses compared to WT. Since Gdf5 expression is increased in Hyp entheses and GDF5 promotes chondrocyte maturation and hypertrophy, we undertook studies to determine the role of GDF5 in Hyp enthesopathy development by deleting Gdf5 globally in Hyp mice (Gdf5KO/Hyp) and conditionally in cells that express Scx (markers of enthesis/tendon) in Hyp mice (Gdf5f/f;ScxCre+/Hyp). In both murine models, Gdf5KO/Hyp and Gdf5f/f;ScxCre+/Hyp entheses had similar significant decreases in immunoreactivity for BMP/IHH signaling markers and ALP activity compared to Hyp and Gdff/f/Hyp controls, respectively. Consistent with these results, mRNA expression of BMP/IHH signaling target genes were significantly decreased in Gdf5f/f;ScxCre+/Hyp entheses compared with Gdff/f/Hyp control entheses. Deletion of Gdf5 in WT mice or in the Scx+ cells of WT mice did not alter BMP /IHH signaling in entheses. Taken together, these data suggest that although GDF5 action is not essential for regulating BMP/IHH signaling in WT entheses, the enhanced Gdf5 expression in Hyp entheses plays a pathogenic role in XLH enthesopathy development. Moreover, GDF5 action in Scx+ cells in Hyp mice regulates the enhanced BMP/IHH signaling seen in Hyp entheses. Blocking BMP/GDF5 signaling may be important in the treatment of XLH enthesopathy. Presentation: 6/1/2024

  PublisherOA PDFDOI

Recent grants

• BMP2 signaling of the development of osetoarthritis

  NIH · $216k · 2013–2016

• Adult Bone Mass Regulation by Type 2 BMP Receptors

  NIH · $2.6M · 2014–2020

• NIH Grant R01AR050174

  NIH · $2.3M · 2010

• BMP2 signaling of the development of osetoarthritis

  NIH · $180k · 2013–2015

• BMP-2 Regulation of Bone Homeostasis

  NIH · $1.9M · 2009–2015

Frequent coauthors

• Laura W. Gamer

  Harvard University

  38 shared

• John M. Wozney

  35 shared

• Karen Cox

  Boston University

  23 shared

• Anthony Celeste

  Boundless Bio (United States)

  17 shared

• Shoichiro Kokabu

  Kyushu Dental University

  15 shared

• Jonathan W. Lowery

  Marian University - Indiana

  15 shared

• Gregory R. Mundy

  14 shared

• Jiake Xu

  Wenzhou Medical University

  14 shared

Awards & honors

• Doctors Samuel and Ida Gelfand Professorship (2024)