Osteoprogenitor cells within skeletal muscle

Abstract

The formation of ectopic bone within skeletal muscle is a widely observed phenomenon. However, the source of the osteoprogenitor cells responsible for ectopic bone formation remains unknown. This study was designed to test for osteogenic differentiation among cells isolated from skeletal muscle tissue. Different subpopulations of cells derived from an adult mouse skeletal muscle were tested for induction of alkaline phosphatase activity after exposure to bone morphogenetic protein-2 in vitro. A responsive subpopulation was identified, transduced with a retrovirus encoding for beta-galactosidase (Rv-lacZ) and an adenoviral construct encoding for one bone morphogenetic protein-2, and injected into the hindlimb of immune compromised (severe combined immunodeficient, or SCID) mice. The injected cells appeared to actively participate in the ectopic bone formation. The existence of lacZ-positive muscle-derived cells colocalized with osteocalcin-producing cells within lacunae of newly formed bone matrix suggests osteoblast and osteocyte differentiation. Although a specific cell was not isolated, these data support the contentions that osteoprogenitor cells reside within skeletal muscle and that muscle may represent a source other than bone marrow for the harvest of these cells.

Deep vein thrombosis and heterotopic ossification in spinal cord injury: a 3 year experience at the Swiss Paraplegic Centre Nottwil

“…21 Indeed elevated levels of osteoblast stimulating factors have been identi®ed in SCI with heterotopic ossi®cation 30 and osteoprogenitor cells have been shown to reside within skeletal muscle. 31 Our ®ndings support the concept of HO as a complex, primarily in¯ammatory process possibly triggered by mechanical (microtraumatic) events. To de®ne the pathogenetic mechanisms responsible for HO, molecular studies (ie gene expression studies) of involved tissues appear necessary.…”

Muscle-derived cell-mediated ex vivo gene therapy for urological dysfunction

“…Furthermore, recent studies have reported that these cells may exist in skeletal muscle. 7,9,[23][24][25][26][27][28][29] The presence of stem cells in skeletal muscle makes this tissue an attractive source of cells that are capable of enhancing the healing of various tissues. 9 In fact, we have recently observed that the genetic engineering of MDC (mc13) to express rhBMP-2 can be used to enhance closure of a non-healing skull defect.…”

“…23 It is now well established that muscle satellite cells are heterogenous and that skeletal muscle tissue may be a source for pluripotent stem cells. 7,9,[24][25][26][27][28][29] In particular, stem cell populations from muscle were recently shown to reconstitute the hematopoietic compartment of lethally irradiated mice and to partially restore the expression of dystrophin in the mdx mouse, an animal model of Duchenne muscular dystrophy. 7 In our laboratory, we have shown that the population of MDC (pp6) was, in fact, multipotent and had the capability of differentiating into other mesenchymal tissues, such as osteogenic lineage.…”

Identifying the Cellular Mechanisms Leading to Heterotopic Ossification

“…These cells fuse and align to form multinucleated primary myofibres. Previous studies have shown that skeletal muscle contains populations of osteoprogenitor cells, with ectopic bone formation being achieved experimentally using solubilised factors obtained from bone [46][47][48]. Evidence of an osteogenic capacity has also been recorded for both rat (L6 cells) and mouse (C2C12 cells) skeletal muscle myoblasts following transfection with osteogenic inducers, such as BMPs [49,50].…”