{"entity": "researcher", "timestamp": "2026-10-18T22:24:11.689Z", "family": "Horkeby", "given": "Karin", "initials": "K", "orcid": "0000-0003-2082-4886", "affiliations": ["Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/f6412d4867264f95a0f56cf6a819498a.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/f6412d4867264f95a0f56cf6a819498a"}}, "publications": [{"entity": "publication", "iuid": "080c969ecfb24db485c82b05fe0b19f7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/080c969ecfb24db485c82b05fe0b19f7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/080c969ecfb24db485c82b05fe0b19f7"}}, "title": "Adrenal-derived factors drive progression of sclerotic prostate cancer in bone.", "authors": [{"family": "Hagberg Thulin", "given": "Malin", "initials": "M", "orcid": "0000-0002-8673-1247", "researcher": {"href": "https://publications.scilifelab.se/researcher/fbf6e0d2d6f748e39f32a70e1e4d597f.json"}}, {"family": "Li", "given": "Lei", "initials": "L"}, {"family": "Abrahamsson", "given": "Sanna", "initials": "S"}, {"family": "Landin", "given": "Andreas", "initials": "A"}, {"family": "Horkeby", "given": "Karin", "initials": "K", "orcid": "0000-0003-2082-4886", "researcher": {"href": "https://publications.scilifelab.se/researcher/f6412d4867264f95a0f56cf6a819498a.json"}}, {"family": "Wu", "given": "Jianyao", "initials": "J"}, {"family": "Lagerquist", "given": "Marie K", "initials": "MK"}, {"family": "Ohlsson", "given": "Claes", "initials": "C"}, {"family": "Poutanen", "given": "Matti", "initials": "M", "orcid": "0000-0002-8953-1734", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ff90a5ebc4d4c91bf7d52caf9841e9e.json"}}], "type": "journal article", "published": "2026-06-01", "journal": {"title": "Endocr. Relat. Cancer", "issn": "1479-6821", "volume": "33", "issue": "6", "issn-l": "1351-0088"}, "abstract": "Bone metastasis is a leading cause of death in prostate cancer (PC) patients. Although androgen deprivation therapy (ADT) combined with novel androgen-targeted agents constitutes the cornerstone of systemic treatment, its efficacy is limited. We investigated the adrenal contribution to promoting progression of castration-resistant PC (CRPC) within bone using a preclinical intratibial xenograft model (VCaP, 22Rv1, and LNCaP cells). Mice underwent orchiectomy (ORX) to mimic ADT, with or without adrenalectomy (ORX + ADX) to eliminate adrenal contribution. A significant increase in bone mineral density (BMD) was observed in tumor-grafted tibiae in ORX-treated mice compared with controls (P < 0.001), indicating a strong tumor-induced sclerotic response. In contrast, ORX + ADX reduced tumor take rate by approximately 50% and decreased tumor-induced BMD by over 80% (P < 0.001). Transcriptomic analysis revealed that ADX downregulated tumor-induced transcripts in bone by over 90%, including osteogenic (Lox, Sparcl1, Bmp2, Postn, and Col1a1) and pro-angiogenic (Bmper, Pecam-1, and Esam) signatures. In addition, BMP, PI3K/Akt, and ERK1/2 signaling pathways were associated with the tumor-induced bone response. Both high serum progesterone and intratumoral levels of dihydrotestosterone (DHT) were associated with the sclerotic bone phenotype. ADX markedly reduced intratumoral DHT and downregulated glycolytic genes (HK2, PFK2, and LDHA) and secretory proteins expressed by the tumor, including stanniocalcin 2, potentially mediating paracrine effects in the sclerotic bone response. Altogether, these findings highlight the critical role of adrenal-dependent androgen synthesis, particularly via progesterone, in driving the sclerotic CRPC in bone. Our findings suggest that a comprehensive blockade of adrenal contribution is essential to prevent the sclerotic bone response associated with CRPC.", "doi": "10.1530/ERC-25-0309", "pmid": "42149634", "labels": {"Clinical Genomics Gothenburg": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC13261362"}, {"db": "pii", "key": "e250309"}], "notes": [], "created": "2026-10-16T15:00:13.764Z", "modified": "2026-10-16T15:00:13.844Z"}, {"entity": "publication", "iuid": "7bdd2bcdaec14360a6b92d1c49b4dc63", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7bdd2bcdaec14360a6b92d1c49b4dc63.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7bdd2bcdaec14360a6b92d1c49b4dc63"}}, "title": "Membrane-initiated estrogen receptor-\u03b1 signaling in the hypothalamus regulates trabecular bone in femur in female mice.", "authors": [{"family": "Jiang", "given": "Yiwen", "initials": "Y"}, {"family": "Horkeby", "given": "Karin", "initials": "K", "orcid": "0000-0003-2082-4886", "researcher": {"href": "https://publications.scilifelab.se/researcher/f6412d4867264f95a0f56cf6a819498a.json"}}, {"family": "Henning", "given": "Petra", "initials": "P"}, {"family": "Nilsson", "given": "Karin H", "initials": "KH"}, {"family": "Wu", "given": "Jianyao", "initials": "J"}, {"family": "Li", "given": "Lei", "initials": "L"}, {"family": "Mov\u00e9rare-Skrtic", "given": "Sofia", "initials": "S"}, {"family": "Ohlsson", "given": "Claes", "initials": "C"}, {"family": "Lagerquist", "given": "Marie K", "initials": "MK"}], "type": "journal article", "published": "2026-05-01", "journal": {"title": "J Endocrinol", "issn": "1479-6805", "volume": "269", "issue": "2", "issn-l": null}, "abstract": "Membrane-initiated estrogen receptor-\u03b1 (mER\u03b1) signaling has been demonstrated to be crucial for normal bone metabolism, and our previous work has confirmed its essential role in osteoblasts. However, the contribution of brain-derived mER\u03b1 signaling to bone homeostasis remains unexplored. To investigate the role of brain-derived mER\u03b1 signaling in bone metabolism, we developed a POMC-C451Af/f mouse model in which mER\u03b1 signaling is selectively inactivated in POMC-expressing neurons. Gonadal-intact female POMC-C451Af/f mice exhibited disturbed sex steroid levels and significantly increased bone mass in both cortical and trabecular compartments compared to littermate C451Af/f controls after sexual maturation (16 weeks old). In ovariectomized female POMC-C451Af/f mice, estradiol (E2) treatment enhanced the anabolic response in trabecular bone of the femur compared to controls, while the estrogen response in cortical bone was similar between the genotypes. Gonadal-intact male POMC-C451Af/f mice displayed altered levels of testosterone compared to controls at 24 weeks of age. In orchiectomized male mice, responses to E2 treatment were similar across all examined parameters between POMC-C451Af/f and control mice. In conclusion, our findings reveal an important role of membrane-initiated ER\u03b1 signaling in POMC neurons in regulating hormone balance and bone metabolism, with more pronounced effects in female mice.", "doi": "10.1530/JOE-25-0462", "pmid": "42133461", "labels": {"Clinical Genomics Gothenburg": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC13192689"}, {"db": "pii", "key": "JOE-25-0462"}], "notes": [], "created": "2026-10-16T15:04:53.856Z", "modified": "2026-10-16T15:04:53.867Z"}, {"entity": "publication", "iuid": "237061eecc404450b373c88ff7e7f8d0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/237061eecc404450b373c88ff7e7f8d0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/237061eecc404450b373c88ff7e7f8d0"}}, "title": "Gut microbiota transplantation from young adult mice fails to restore low bone and muscle mass in old mice.", "authors": [{"family": "Lawenius", "given": "Lina", "initials": "L", "orcid": "0009-0001-6261-6412", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f57a6c07ded48af88ead664d0fbd6da.json"}}, {"family": "H\u00e4gg", "given": "Daniel", "initials": "D"}, {"family": "Horkeby", "given": "Karin", "initials": "K", "orcid": "0000-0003-2082-4886", "researcher": {"href": "https://publications.scilifelab.se/researcher/f6412d4867264f95a0f56cf6a819498a.json"}}, {"family": "Nilsson", "given": "Karin H", "initials": "KH", "orcid": "0000-0001-9341-7400", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d78a51878ad44589ccb1197366026fc.json"}}, {"family": "Wu", "given": "Jianyao", "initials": "J"}, {"family": "Grahnemo", "given": "Louise", "initials": "L", "orcid": "0000-0001-5276-6612", "researcher": {"href": "https://publications.scilifelab.se/researcher/bb1ac8fe74954a5db43e8e6538cf8235.json"}}, {"family": "Ohlsson", "given": "Claes", "initials": "C", "orcid": "0000-0002-9633-2805", "researcher": {"href": "https://publications.scilifelab.se/researcher/995dac358caa4a169fc889b7a3eef44a.json"}}, {"family": "Sj\u00f6gren", "given": "Klara", "initials": "K", "orcid": "0000-0001-5776-7278", "researcher": {"href": "https://publications.scilifelab.se/researcher/0168b5f57a9c466690272b382561fcb8.json"}}], "type": "journal article", "published": "2026-04-01", "journal": {"title": "Am J Physiol Endocrinol Metab", "issn": "1522-1555", "volume": "330", "issue": "4", "pages": "E461-E470", "issn-l": null}, "abstract": "Aging is associated with reduced lean and bone mass, as well as alterations in gut microbiota composition. We previously demonstrated that gut microbiota composition differs between young adult and old mice, and that transplanting gut microbiota from old donors into young germ-free mice reduces lean mass, but not bone mass, compared with transplantation from young adult donors. In this study, we investigated whether the reduced lean and bone mass observed in old mice could be restored through gut microbiota transplantation from young adult donors. Old mice (18-mo old) were treated with antibiotics to deplete their gut microbiota and subsequently transplanted with gut microbiota from either young adult (5-mo old) or old (21-mo old) donors. Recipient mice colonized with gut microbiota from young adult donors showed distinct beta and alpha diversity compared with those colonized with gut microbiota from old donors, demonstrating successful transplantation. However, no differences in lean or bone mass were observed between old mice transplanted with gut microbiota from young adult donors and those receiving gut microbiota from old donors. In conclusion, our findings demonstrate that gut microbiota composition differs in mice transplanted with young adult compared with old gut microbiota but neither reduced lean mass nor reduced bone mass in old mice can be restored through gut microbiota transplantation from young adult donors.NEW & NOTEWORTHY Aging is associated with reduced lean and bone mass and changes in gut microbiota (GM). We tested whether transplanting young adult GM could reverse these age-related conditions in old mice. GM transplantation resulted in distinct GM compositions between mice receiving young adult versus old donor GM, but neither lean nor bone mass was restored in old mice. These findings suggest that GM from young adult mice cannot restore musculoskeletal deficits in aging.", "doi": "10.1152/ajpendo.00522.2025", "pmid": "41778924", "labels": {"Clinical Genomics Gothenburg": "Service", "Clinical Genomics": "Service"}, "xrefs": [], "notes": [], "created": "2026-10-16T15:04:21.262Z", "modified": "2026-10-16T15:04:21.391Z"}]}