{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:20:59Z","timestamp":1784557259984,"version":"3.55.0"},"reference-count":106,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:p>\n                    Impaired resorption of cartilage matrix deposited during endochondral ossification is a defining feature of juvenile osteopetrosis. Growing, leptin-deficient\n                    <jats:italic>ob\/ob<\/jats:italic>\n                    mice exhibit a mild form of osteopetrosis. However, the extent to which the disease is (1) self-limiting and (2) reversible by leptin treatment is unknown. We addressed the first question by performing histomorphometric analysis of femurs in rapidly growing (2-month-old), slowly growing (4-month-old) and skeletally mature (6-month-old) wild-type (WT) and\n                    <jats:italic>ob\/ob<\/jats:italic>\n                    male mice. Absent by 6 months of age in WT mice, cartilage matrix persisted to varying extents in distal femur epiphysis, metaphysis and diaphysis in\n                    <jats:italic>ob\/ob<\/jats:italic>\n                    mice, suggesting that the osteopetrotic phenotype is not entirely self-limiting. To address the second question, we employed hypothalamic recombinant adeno-associated virus (rAAV) gene therapy to restore leptin signaling in\n                    <jats:italic>ob\/ob<\/jats:italic>\n                    mice. Two-month-old mice were randomized to one of the three groups: (1) untreated control, (2) rAAV-Leptin or (3) control vector rAAV-green fluorescent protein and vectors injected intracerebroventricularly. Seven months later, rAAV-leptin-treated mice exhibited no cartilage in the metaphysis and greatly reduced cartilage in the epiphysis and diaphysis. At the cellular level, the reduction in cartilage was associated with increased bone turnover. These findings (1) support the concept that leptin is important for normal replacement of cartilage by bone, and (2) demonstrate that osteopetrosis in\n                    <jats:italic>ob\/ob<\/jats:italic>\n                    mice is bone-compartment-specific and reversible by leptin at skeletal sites capable of undergoing robust bone turnover.\n                  <\/jats:p>","DOI":"10.1530\/joe-17-0524","type":"journal-article","created":{"date-parts":[[2017,11,30]],"date-time":"2017-11-30T20:11:07Z","timestamp":1512072667000},"page":"57-68","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":14,"title":["Effects of hypothalamic leptin gene therapy on osteopetrosis in leptin-deficient mice"],"prefix":"10.1530","volume":"236","author":[{"given":"Kenneth A","family":"Philbrick","sequence":"first","affiliation":[{"name":"1Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen A","family":"Martin","sequence":"additional","affiliation":[{"name":"1Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy R","family":"Colagiovanni","sequence":"additional","affiliation":[{"name":"1Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam J","family":"Branscum","sequence":"additional","affiliation":[{"name":"2Biostatistics Program, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell T","family":"Turner","sequence":"additional","affiliation":[{"name":"1Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USA"},{"name":"3Center for Healthy Aging Research, Oregon State University, Corvallis, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urszula T","family":"Iwaniec","sequence":"additional","affiliation":[{"name":"1Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USA"},{"name":"3Center for Healthy Aging Research, Oregon State University, Corvallis, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref371","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1530\/JOE-16-0484","article-title":"Leptin stimulates bone formation in ob\/ob mice at doses having minimal impact on energy metabolism","volume":"232","year":"2017","journal-title":"Journal of 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